Abstract

Mast cells are long-lived, innate immune cells of the myeloid lineage which are found in peripheral tissues located throughout the body, and positioned at the interface between the host and the environment. Mast cells are found in high concentrations during helminth infection. Using Kitw-sh mast cell deficient mice, a recently published study in Bioscience Reports by Gonzalez et al. (Biosci. Rep., 2018) focused on the role of mast cells in the immune response to infection by the helminth Hymenolepis diminuta. The authors showed that mast cells play a role in the modulation of Th2 immune response characterized by a unique IL-4, IL-5 and IL-13 cytokine profile, as well as subsequent robust worm expulsion during H. diminuta infection. Unlike WT mice which expelled H. diminuta at day 10, Kitw-sh deficient mice displayed delayed worm expulsion (day 14 post infection). Further, a possible role for mast cells in the basal expression of cytokines IL-25, IL-33 and thymic stromal lymphopoietin was described. Deletion of neutrophils in Kitw-sh deficient mice enhanced H. diminuta expulsion, which was accompanied by splenomegaly. However, interactions between mast cells and other innate and adaptive immune cells during helminth infections are yet to be fully clarified. We conclude that the elucidation of mechanisms underlying mast cell interactions with cells of the innate and adaptive immune system during infection by helminths can potentially uncover novel therapeutic applications against inflammatory, autoimmune and neoplastic diseases.

Mast cells (MC) are long-lived, granulated, tissue resident effector cells of hematopoietic origin, recognized for their role in allergic inflammation and immunity to parasitic infection. They derive from common myeloid progenitors in the bone marrow, and continue their development through the granulocyte/monocyte progenitor lineage. Development into MC progenitors in the bone marrow is highly regulated by transcription factors. Cells committed to the MC lineage leave the bone marrow as MC progenitors, and circulate in the bloodstream before homing to peripheral tissues including the skin, lung, peritoneum and the intestinal epithelia [1]. Two major subsets have been identified: connective tissue MCs and mucosal MCs. Mast cell development and survival are dependent on the surface expression of the receptor tyrosine kinase c-kit, present in the W-locus (chromosome 5) in mice. C-kit is a receptor for the ligand, stem cell factor (SCF), an important growth factor for MC. Indeed, mutations at the c-kit locus have been used extensively for the study of MC deficiency in mice. For example, mice with the W-sh mutation (KitW-sh/W-sh) which possess an inversion mutation in the transcriptional regulatory region of the c-kit gene [2] results in a significant reduction in c-kit mRNA and subsequently MC deficiency in peripheral tissues. In addition to mutant Kit-based mast cell deficient mice, (KitW-sh/W-sh and WBB6F1-KitW/Wv), genetically modified mouse models such as Mcpt5Cre and Cpa3Cre have been shown to be useful in addressing the function of MC in vivo [3].

MCs are known mediators of anti-helminthic responses such as infections with Heligmosomoides polygyrus, Trichuris suis, Schistosoma japonicum, Necator americanus, Strongyloides venezuelensis, Trichinella spiralis and Trichuris muris [4–11] (Table 1). In the context of helminthic infection, the effector functions of MC are largely mediated by high affinity interactions of the IgE receptor, FcεR1 present on MC. Interaction between IgE and FcεR1 results in the activation and subsequent release of cytosolic granules by MC. These granules contain a number of cytokines, growth factors, and proteases including interleukin (IL)-4, IL-5, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF) and mast cell protease 1 (MCPT-1), which can be detected as free MCPT-1 in the serum or tissues as an indicator for the presence of MC in vivo [12]. Helminthic infections trigger a number of host responses, largely characterized by a Th2 polarized immune response. In response to helminth infection, innate immune cells and intestinal epithelial cells secrete Th2 cytokines including IL-4, IL-5, IL-9, IL-13, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) [13]. IL-33, a cytokine released during helminth infection, causes the activation and proliferation of MC through interaction with the ST2 receptor [14,15]. Activation of MC results in their degranulation and release of pre-formed mediators known to modulate cells of the innate and adaptive immune system. Among these are IL-4 and IL-13 resulting in the alternative activation of macrophages [16], prostaglandin D2, which cleaves IL-33 resulting in increased type 2 innate lymphoid cell induction through CRTH2 receptor interaction [17], and TNF-α, CXCL1 and CXCL2 leading to the recruitment and proliferation of neutrophils at the site of infection [18,19]. TNF-α mediated neutrophil recruitment by MC has further been shown to be at least partially dependent MC activation by IL-33 [19]. In addition to the activation and recruitment of cells of the innate and adaptive immune system, MC degranulation induces effector mechanisms involved in worm expulsion such as goblet cell hyperplasia, increased mucin production, mitigation of tissue damage, intestinal smooth muscle contraction associated with heightened peristalsis, and the creation of an environment toxic to helminths [20]. Although MCs are known mediators of the helminth associated Th2 response, it is evident that their roles vary, depending on the host, parasite dose, parasite life cycle stage, and duration of infection [21].

Table 1
Helminthic infections: role of mast cells and suppression of autoimmune inflammatory diseases
Helminth MC involvement in helminth infection Amelioration of inflammatory disease 
  Disease Model 
Hymenolepis diminuta (Rat Tapeworm) MC contributes to helminth expulsion DNBS/DSS colitis [22,23,44–47Experimental (Mouse) 
 [24,43Autism [48Clinical 
  Arthritis [49Experimental (Mouse) 
Trichuris suis (Pig Whipworm) MC accumulates during infection [9DSS colitis [50Experimental (Rabbit) 
  EAE [51Experimental 
  OVA-sensitization [52Experimental (Mouse) 
  Ulcerative colitis [53,54Clinical trial 
  Crohn’s disease [54–56Clinical trial 
  Multiple sclerosis [57Clinical trial 
  Allergic rhinitis [58Clinical trial 
  Peanut/Treenut allergy [59Clinical trial 
  Plaque psoriasis [60Clinical trial 
  Autism [48,61Clinical trial 
Necator americanus (Human Hookworm) MC accumulation and degranulation Crohn’s disease [62Clinical trial 
 correlate with protection against helminth Celiac disease [63Clinical trial 
 [10Asthma [64–66Clinical trial 
  Multiple sclerosis [67Clinical trial 
  Allergic rhinitis [68Clinical trial 
Trichuris trichuria (Human Whipworm) Not studied Ulcerative colitis [69Clinical trial 
  Atopic dermatitis [70Clinical trial 
  Multiple sclerosis [71Clinical trial 
Schistosoma mansoni Conflicting data; most evidence suggest EAE [76,77Experimental (Mouse) 
 that MC accumulation correlates with NOD [78,79Experimental (Mouse) 
 susceptibility to infection [72–75TNBS/DSS colitis [80–82Experimental (Mouse, Rat) 
  OVA-sensitization [83,84Experimental (Mouse) 
  Anaphylaxis [85Experimental (Mouse) 
  TSHR (Graves’ disease) [86Experimental (Mouse) 
  CIA [87Experimental (Mouse) 
Trichinella spiralis Apparent involvement of MC in helminth EAE [90–92Experimental (Rat) 
 expulsion [88,89NOD [93Experimental (Mouse) 
  DNBS colitis [94–97Experimental (Mouse) 
Heligmosomoides polygyrus MC play a major role in clearance of EAE [100Experimental (Mouse) 
 infection [98,99NOD [93Experimental (Mouse) 
  IBD [101–103Experimental (Mouse) 
  OVA-sensitization [100,104,105Experimental (Mouse) 
  Arthritis [106Experimental (Mouse) 
  Peanut allergy [107Experimental (Mouse) 
  TNBS colitis [108,109Experimental (Mouse) 
Trichinella pseudospiralis MC accumulates during infection [110EAE [111Experimental (Mouse) 
Taenia crassiceps MC accumulates during infection [112MLDS [113Experimental (Mouse) 
  EAE [114Experimental (Mouse) 
  DSS colitis [115Experimental (Mouse) 
Litomosoides sigmodontis MC degranulation promotes helminth NOD [118,119Experimental (Mouse) 
 invasion and survival in host [116,117OVA-sensitization [120Experimental (Mouse) 
  DIO [121Experimental (Mouse) 
Ancylostoma caninum MC accumulates during infection [122DSS colitis [123Experimental (Mouse) 
Strongyloides venezuelensis MC play a major role in clearance of infection [124,125MLDS [126Experimental (Mouse) 
Nippostrongylus brasiliensis MC contributes to helminth expulsion OVA-sensitization [128Experimental (Mouse) 
 [127Arthritis [106Experimental (Mouse) 
Schistosoma japonicum MC accumulates during infection [11OVA-sensitization [129,130Experimental (Mouse) 
  TNBS colitis [131Experimental (Mouse) 
  EAE [132Experimental (Mouse) 
Trichuris muris MC accumulates but not required for DSS colitis [136Experimental (Mouse) 
 protection against infection [133–135AAI [137Experimental (Mouse) 
Helminth MC involvement in helminth infection Amelioration of inflammatory disease 
  Disease Model 
Hymenolepis diminuta (Rat Tapeworm) MC contributes to helminth expulsion DNBS/DSS colitis [22,23,44–47Experimental (Mouse) 
 [24,43Autism [48Clinical 
  Arthritis [49Experimental (Mouse) 
Trichuris suis (Pig Whipworm) MC accumulates during infection [9DSS colitis [50Experimental (Rabbit) 
  EAE [51Experimental 
  OVA-sensitization [52Experimental (Mouse) 
  Ulcerative colitis [53,54Clinical trial 
  Crohn’s disease [54–56Clinical trial 
  Multiple sclerosis [57Clinical trial 
  Allergic rhinitis [58Clinical trial 
  Peanut/Treenut allergy [59Clinical trial 
  Plaque psoriasis [60Clinical trial 
  Autism [48,61Clinical trial 
Necator americanus (Human Hookworm) MC accumulation and degranulation Crohn’s disease [62Clinical trial 
 correlate with protection against helminth Celiac disease [63Clinical trial 
 [10Asthma [64–66Clinical trial 
  Multiple sclerosis [67Clinical trial 
  Allergic rhinitis [68Clinical trial 
Trichuris trichuria (Human Whipworm) Not studied Ulcerative colitis [69Clinical trial 
  Atopic dermatitis [70Clinical trial 
  Multiple sclerosis [71Clinical trial 
Schistosoma mansoni Conflicting data; most evidence suggest EAE [76,77Experimental (Mouse) 
 that MC accumulation correlates with NOD [78,79Experimental (Mouse) 
 susceptibility to infection [72–75TNBS/DSS colitis [80–82Experimental (Mouse, Rat) 
  OVA-sensitization [83,84Experimental (Mouse) 
  Anaphylaxis [85Experimental (Mouse) 
  TSHR (Graves’ disease) [86Experimental (Mouse) 
  CIA [87Experimental (Mouse) 
Trichinella spiralis Apparent involvement of MC in helminth EAE [90–92Experimental (Rat) 
 expulsion [88,89NOD [93Experimental (Mouse) 
  DNBS colitis [94–97Experimental (Mouse) 
Heligmosomoides polygyrus MC play a major role in clearance of EAE [100Experimental (Mouse) 
 infection [98,99NOD [93Experimental (Mouse) 
  IBD [101–103Experimental (Mouse) 
  OVA-sensitization [100,104,105Experimental (Mouse) 
  Arthritis [106Experimental (Mouse) 
  Peanut allergy [107Experimental (Mouse) 
  TNBS colitis [108,109Experimental (Mouse) 
Trichinella pseudospiralis MC accumulates during infection [110EAE [111Experimental (Mouse) 
Taenia crassiceps MC accumulates during infection [112MLDS [113Experimental (Mouse) 
  EAE [114Experimental (Mouse) 
  DSS colitis [115Experimental (Mouse) 
Litomosoides sigmodontis MC degranulation promotes helminth NOD [118,119Experimental (Mouse) 
 invasion and survival in host [116,117OVA-sensitization [120Experimental (Mouse) 
  DIO [121Experimental (Mouse) 
Ancylostoma caninum MC accumulates during infection [122DSS colitis [123Experimental (Mouse) 
Strongyloides venezuelensis MC play a major role in clearance of infection [124,125MLDS [126Experimental (Mouse) 
Nippostrongylus brasiliensis MC contributes to helminth expulsion OVA-sensitization [128Experimental (Mouse) 
 [127Arthritis [106Experimental (Mouse) 
Schistosoma japonicum MC accumulates during infection [11OVA-sensitization [129,130Experimental (Mouse) 
  TNBS colitis [131Experimental (Mouse) 
  EAE [132Experimental (Mouse) 
Trichuris muris MC accumulates but not required for DSS colitis [136Experimental (Mouse) 
 protection against infection [133–135AAI [137Experimental (Mouse) 

Infection of the rat tapeworm Hymenolepis diminuta in mice is an established model system used to elucidate the complex immune response mechanisms to chronic intestinal helminthic infections in humans. Because these tapeworms possess potent immunosuppressive properties during concomitant inflammatory disease states (such as colitis), and are known to cause minimal to no tissue damage within the host they are ideal models for the study of helminth-associated immunological responses [22]. Not surprisingly, the immunomodulatory and anti-inflammatory properties of H. diminuta are potentially being exploited in the treatment of gut-associated inflammatory diseases – an area currently known as ‘helminth therapy’ which is currently under active investigation [23].

Given our limited understanding of the specific roles of MC during infection with H. diminuta, the study by González et al. [24] begins to define the immunomodulatory function of MC against this helminth in vivo. Mice are known to generate a strong Th2 polarized immune response against H. diminuta and clear infection in 8–10 days [25]. Using C57BL/6 mice with KitW-sh/W-sh mutations, which depletes MC [26], a revealing picture is beginning to emerge suggesting a role for MC in effective elimination of H. diminuta from infected hosts. Previous studies involving infection by H. diminuta have followed MC activity using rat models, which generate a wide array of MC activation profiles dependent upon helminth dose and rat species, making the elucidation of MC effects on elimination of helminths from the gut lumen challenging [27]. In mice, activation of MC in response to H. diminuta infection has been demonstrated as indicated by the detection of MCPT-1, a MC biomarker detectable in serum [28]. KitW-sh/W-sh mice lacking in a MC response as shown through the non-detectable levels of serum MCPT-1 have been used previously to demonstrate the wide ranging effects that MC can have in mediating an effective Th2 polarized anti-helminthic immune response in vivo [29]. During H. diminuta infection, KitW-sh/W-sh mice produced an altered Th2 cytokine immune response profile, which differed in kinetics compared with infected WT mice. Interestingly, infected KitW-sh/W-sh mice produced higher quantities of IL-4 and IL-13 at day 4, but lower levels at day 8 compared with infected WT controls. Levels of these cytokines are again reversed at day 12, with an apparent rebound in IL-4 and IL-13 production in infected KitW-sh/W-sh mice. While this altered Th2 cytokine profile in infected KitW-sh/W-sh mice appears to be MC dependent, additional studies are needed to determine the mechanisms underlying the unique kinetics of Th2 cytokine production during H. diminuta infection of KitW-sh/W-sh mice. Nevertheless, these results suggest a role for activated MC in modulating Th2 cytokine production during H. diminuta infection, [30]. It must be noted, however, that while non-detectable levels of MCPT-1 are strongly indicative of complete absence of MC (which was used as a surrogate for MC in the study by Gonzalez et al. [24]), there have been demonstrated instances of a MC presence occurring in Kit-deficient animals [31,32]. Nevertheless, the delayed worm expulsion seen experimentally does demonstrate an as yet unknown role for MC in the optimal generation of an effective immune response against H. diminuta.

In addition to the aforementioned cytokines (IL-4, IL-5 and IL-13), González et al. [24] found that basal expression of epithelia derived cytokines IL-25, IL-33, and TSLP in uninfected KitW-sh/W-sh deficient mice was lower compared with uninfected WT controls. This suggests a role for MC maintaining homeostatic basal expression for these cytokines. Previous research performed using different helminth models demonstrates a role for MC in the production of IL-25, IL-33, and TSLP, suggesting the possibility of MC priming of these cytokines during early infection [4]. In H. diminuta infected mice, expression values were similar for these cytokines, indicating that while MC may assist in the maintenance of their basal expression, these cytokines can still be induced independent of MC during this helminth infection. While a clearer picture of the regulation of these epithelium derived cytokines is beginning to emerge, the precise immunologic mechanisms that underlie their production and regulation are still incompletely understood [33]. Increased expression of these cytokines has been linked to the allergic and asthma response [34], and a mechanism decreasing basal IL-25, IL-33 and TSLP expression may be of interest in potential therapy development. Importantly, these cytokines have each recently been attributed to having an important initial role in inducing a microenvironment suitable for Th2 polarization [35]. This correlation between reductions in these epithelial derived cytokines and the delayed Th2 response seen experimentally is further evidence in support of the Th2 polarizing effect of IL-25, IL-33 and TSLP in certain helminthic infections. Further research into the immunomodulatory roles and regulatory mechanisms of these epithelial derived cytokines, as well as their cross-talk with MCs during inflammation will provide insights into therapeutic approaches in the management of helminthic, gut-inflammatory and allergic diseases.

A clear understanding of the interaction between MCs and other innate and adaptive immune cells during helminthic infection is vitally important in order to clarify the nature of an effective anti-helminthic immune response. For example, the proportion of neutrophils was observed to be increased in the spleens of MC deficient H. diminuta infected mice. However, contrary to the notion that neutrophils could compensate for the lack of MC to confer protection against H. diminuta infection, Gonzalez et al. [24] found that depletion of neutrophils by intraperitoneal administration of anti-Gr-1 antibodies resulted in enhanced clearance of the worm at a rate comparable to infected WT mice. Furthermore, neutrophil depletion in MC deficient H. diminuta infected mice was accompanied by increased splenomegaly. These data present very interesting observations that warrant further study. While it has been previously shown that in vivo depletion of neutrophils can result in a more strongly polarized Th2 response in the context of helminth infection, the mechanisms that underlie this immunological response are not completely understood [36]. Further, in contrast with the data presented by Gonzalez et al. [24], neutrophil depletion in mice during Nippostrongylus brasiliensis helminth infection resulted in a decreased Th2 response and an increased susceptibility to infection [37]. These observations further support the wide variety and complexity of cellular interactions and immunological responses elicited by different helminth infections in vivo. As is the case with other parasitic diseases, infections with helminths require a consideration of pathogen and host associated factors in order to fully explain mechanisms of action and host immune response pathways. In the context of MC inhibition, it would be of interest to determine the impact of neutrophil depletion on immune response to other helminth infections.

As mentioned at the outset, the concept of helminth-based therapy exploits the immunosuppressive properties of helminth species to reduce the severity of gut associated inflammatory diseases. A summary of pre-clinical and clinical studies utilizing helminth parasites to mitigate inflammatory associated diseases is shown in Table 1. In the context of helminth infection by H. diminuta, a protective effect has been demonstrated against colitis in the affected host [23]. However, the relative contribution of immune cells in mitigating the Th1-dominated inflammatory response during helminth-mediated suppression of gut inflammatory diseases is unclear. Given that MCs modulate Th2 responses during H. diminuta infection, it was of interest to determine whether these cells contribute to protection against dinitrobenzene sulfonic acid (DNBS) induced colitis in H. diminuta infected mice. DNBS has been used as an effective agent to recapitulate colitis in vivo [38]. Using this DNBS-induced colitis model, it was observed that both MC deficient and WT mice infected with H. diminuta maintained similar heightened levels of protection against colitis compared with uninfected mice, suggesting that MCs do not play any major role in this protection. Other studies have demonstrated that the epithelial-derived cytokine IL-25 mediates the anti-inflammatory protection by H. diminuta in DNBS-induced colitis [39]. However, it is likely that the protection against colitis exhibited by H. diminuta and partly mediated by IL-25 occurs independent of MC. Other factors might include an involvement of regulatory T cells and/or other myeloid cells involved in promoting a Th2 response caused by the presence of the worm. These and other possibilities provide exciting areas for additional research.

In conclusion, the study by González et al. [24] has increased our understanding of the host cellular factors involved in immune responses against H. diminuta. Results from the present study demonstrate that MCs do contribute to the timely expulsion of H. diminuta. Further, MC-deficient animals display an altered cytokine expression kinetic profile resulting in a delayed expulsion of intestinal helminths. The authors also suggest that MCs are involved in the basal expression of IL-25, IL-33 and TSLP by epithelial cells (Figure 1). A key question remains regarding the degree of MC depletion in KitW-sh/W-sh mice during H. diminuta infection and what subset of MCs (mucosal MCs and/or connective tissue MCs) are depleted in this model. Nevertheless, it is clear that MC mediated immunoregulation during helminth infection is of great interest, given that the strong Th2 immune response generated during infection by helminths has been linked to a positive prognosis or shown to have a beneficial effect in many autoimmune and neoplastic diseases [40–42]. Consequently, therapeutic applications developed as a result of an increased understanding of helminth-associated immunomodulation, as well as the involvement of MCs in response to helminth infection, remains an appealing and worthwhile goal.

Proposed mechanism for the action of mast cells during the immunological response to helminth infection by Hymenolepis diminuta

Figure 1
Proposed mechanism for the action of mast cells during the immunological response to helminth infection by Hymenolepis diminuta

Mast cells stimulate intestinal epithelial cells causing a constitutive expression of basal IL-25, IL-33 and TSLP. The presence of these cytokines in the intestinal lumen is crucial to an efficient immune response required for timely expulsion of helminths. Detection of helminths by the epithelial cells cause an increased release of cytokines IL-25, IL-33 and TSLP, resulting in the activation of mast cells and other Th2 lymphoid and myeloid progenitors. Mast cells secrete a wide variety of cytokines and growth factors including IL-4, IL-5, IL-13, IL-25, IL-33, TNF-α, CXCL1, CXCL2, and TSLP, MCPT-1, prostaglandin D2, and lysozyme. CXCL1, CXCL2 and TNF-α activates neutrophils, prostaglandin D2 production activates type 2 innate lymphoid cells, while IL-4, IL-5 and IL-13 activates alternatively activated macrophages. Mast cell derived IL-25 stimulates the Th2 immune response. Further, mast cell degranulation results in anti-helminthic effector mechanisms including goblet cell hyperplasia, increased mucin production, smooth muscle contraction and increased peristalsis, leading to helminth expulsion.

Figure 1
Proposed mechanism for the action of mast cells during the immunological response to helminth infection by Hymenolepis diminuta

Mast cells stimulate intestinal epithelial cells causing a constitutive expression of basal IL-25, IL-33 and TSLP. The presence of these cytokines in the intestinal lumen is crucial to an efficient immune response required for timely expulsion of helminths. Detection of helminths by the epithelial cells cause an increased release of cytokines IL-25, IL-33 and TSLP, resulting in the activation of mast cells and other Th2 lymphoid and myeloid progenitors. Mast cells secrete a wide variety of cytokines and growth factors including IL-4, IL-5, IL-13, IL-25, IL-33, TNF-α, CXCL1, CXCL2, and TSLP, MCPT-1, prostaglandin D2, and lysozyme. CXCL1, CXCL2 and TNF-α activates neutrophils, prostaglandin D2 production activates type 2 innate lymphoid cells, while IL-4, IL-5 and IL-13 activates alternatively activated macrophages. Mast cell derived IL-25 stimulates the Th2 immune response. Further, mast cell degranulation results in anti-helminthic effector mechanisms including goblet cell hyperplasia, increased mucin production, smooth muscle contraction and increased peristalsis, leading to helminth expulsion.

Competing Interests

The authors declare that there are no competing interests associated with the manuscript.

Funding

This work was supported by the National Institute of Health (NIH), National Cancer Institute (NCI) [grant number K01CA207599 (to S.O.)].

Author Contribution

N.M.R. and S.O. wrote the manuscript.

Abbreviations

     
  • AAI

    allergic airway inflammation

  •  
  • CIA

    collagen-induced arthritis

  •  
  • DIO

    diet-induced obesity

  •  
  • DNBS

    dinitrobenzene sulfonic acid

  •  
  • DSS

    dextran sulfate sodium

  •  
  • EAE

    experimental autoimmune encephalomyelitis

  •  
  • IL

    interleukin

  •  
  • MC

    mast cell

  •  
  • MCPT-1

    mast cell protease 1

  •  
  • MLDS

    multiple low-dose streptozotocin-induced diabetes

  •  
  • NOD

    non-obese diabetic

  •  
  • OVA

    ovalbumin

  •  
  • TNBS

    trinitrobenzene sulfonic acid

  •  
  • TNF

    tumor necrosis factor

  •  
  • TSHR

    thyroid stimulating hormone receptor

  •  
  • TSLP

    thymic stromal lymphopoietin

  •  
  • VEGF

    vascular endothelial growth factor

References

References
1.
Dahlin
J.S.
and
Hallgren
J.
(
2015
)
Mast cell progenitors: origin, development and migration to tissues
.
Mol. Immunol.
63
,
9
17
[PubMed]
2.
Nagle
D.L.
,
Kozak
C.A.
,
Mano
H.
,
Chapman
V.M.
and
Bucan
M.
(
1995
)
Physical mapping of the Tec and Gabrb1 loci reveals that the Wsh mutation on mouse chromosome 5 is associated with an inversion
.
Hum. Mol. Genet.
4
,
2073
2079
[PubMed]
3.
Behrends
D.A.
,
Cheng
L.
,
Sullivan
M.B.
,
Wang
M.H.
,
Roby
G.B.
,
Zayed
N.
et al.
(
2014
)
Defective bone repair in mast cell deficient mice with c-Kit loss of function
.
Eur. Cells Mater.
28
,
209
221
,
discussion 221-202
4.
Hepworth
M.R.
,
Danilowicz-Luebert
E.
,
Rausch
S.
,
Metz
M.
,
Klotz
C.
,
Maurer
M.
et al.
(
2012
)
Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines
.
Proc. Natl. Acad. Sci. U.S.A.
109
,
6644
6649
[PubMed]
5.
Martin
R.K.
,
Damle
S.R.
,
Valentine
Y.A.
,
Zellner
M.P.
,
James
B.N.
,
Lownik
J.C.
et al.
(
2018
)
B1 cell IgE impedes mast cell-mediated enhancement of parasite expulsion through B2 IgE blockade
.
Cell Rep.
22
,
1824
1834
[PubMed]
6.
Lantz
C.S.
,
Boesiger
J.
,
Song
C.H.
,
Mach
N.
,
Kobayashi
T.
,
Mulligan
R.C.
et al.
(
1998
)
Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites
.
Nature
392
,
90
93
[PubMed]
7.
Knight
P.A.
,
Wright
S.H.
,
Lawrence
C.E.
,
Paterson
Y.Y.
and
Miller
H.R.
(
2000
)
Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1
.
J. Exp. Med.
192
,
1849
1856
[PubMed]
8.
Reitz
M.
,
Brunn
M.L.
,
Rodewald
H.R.
,
Feyerabend
T.B.
,
Roers
A.
,
Dudeck
A.
et al.
(
2017
)
Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection
.
Mucosal Immunol.
10
,
481
492
[PubMed]
9.
Kringel
H.
,
Iburg
T.
,
Dawson
H.
,
Aasted
B.
and
Roepstorff
A.
(
2006
)
A time course study of immunological responses in Trichuris suis infected pigs demonstrates induction of a local type 2 response associated with worm burden
.
Int. J. Parasitol.
36
,
915
924
[PubMed]
10.
Girod
N.
,
Brown
A.
,
Pritchard
D.I.
and
Billett
E.E.
(
2003
)
Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response
.
Int. J. Parasitol.
33
,
71
80
[PubMed]
11.
Birck
M.M.
,
Pors
S.
,
Johansen
M.V.
and
Iburg
T.
(
2006
)
Distribution of mast cells in relation to Schistosoma japonicum induced lesions in pigs
.
Southeast Asian J. Trop. Med. Public Health
37
,
630
640
[PubMed]
12.
Wernersson
S.
and
Pejler
G.
(
2014
)
Mast cell secretory granules: armed for battle
.
Nat. Rev. Immunol.
14
,
478
494
[PubMed]
13.
Cortes
A.
,
Munoz-Antoli
C.
,
Esteban
J.G.
and
Toledo
R.
(
2017
)
Th2 and Th1 responses: clear and hidden sides of immunity against intestinal helminths
.
Trends Parasitol.
33
,
678
693
[PubMed]
14.
Lopes
F.
,
Reyes
J.L.
,
Wang
A.
,
Leung
G.
and
McKay
D.M.
(
2015
)
Enteric epithelial cells support growth of Hymenolepis diminuta in vitro and trigger TH2-promoting events in a species-specific manner
.
Int. J. Parasitol.
45
,
691
696
[PubMed]
15.
Cayrol
C.
and
Girard
J.P.
(
2018
)
Interleukin-33 (IL-33): a nuclear cytokine from the IL-1 family
.
Immunol. Rev.
281
,
154
168
[PubMed]
16.
Fairweather
D.
and
Cihakova
D.
(
2009
)
Alternatively activated macrophages in infection and autoimmunity
.
J. Autoimmun.
33
,
222
230
[PubMed]
17.
Webb
L.M.
and
Tait Wojno
E.D.
(
2017
)
The role of rare innate immune cells in Type 2 immune activation against parasitic helminths
.
Parasitology
144
,
1288
1301
[PubMed]
18.
De Filippo
K.
,
Dudeck
A.
,
Hasenberg
M.
,
Nye
E.
,
van Rooijen
N.
,
Hartmann
K.
et al.
(
2013
)
Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation
.
Blood
121
,
4930
4937
[PubMed]
19.
Enoksson
M.
,
Moller-Westerberg
C.
,
Wicher
G.
,
Fallon
P.G.
,
Forsberg-Nilsson
K.
,
Lunderius-Andersson
C.
et al.
(
2013
)
Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent
.
Blood
121
,
530
536
[PubMed]
20.
Mukai
K.
,
Tsai
M.
,
Starkl
P.
,
Marichal
T.
and
Galli
S.J.
(
2016
)
IgE and mast cells in host defense against parasites and venoms
.
Semin. Immunopathol.
38
,
581
603
21.
Raina
K.
,
Kumar
S.
,
Dhar
D.
and
Agarwal
R.
(
2016
)
Silibinin and colorectal cancer chemoprevention: a comprehensive review on mechanisms and efficacy
.
J. Biomed. Res.
30
,
452
465
[PubMed]
22.
Reyes
J.L.
,
Wang
A.
,
Fernando
M.R.
,
Graepel
R.
,
Leung
G.
,
van Rooijen
N.
et al.
(
2015
)
Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages
.
J. Immunol.
194
,
364
378
23.
Melon
A.
,
Wang
A.
,
Phan
V.
and
McKay
D.M.
(
2010
)
Infection with Hymenolepis diminuta is more effective than daily corticosteroids in blocking chemically induced colitis in mice
.
J. Biomed. Biotechnol.
2010
,
384523
[PubMed]
24.
Gonzalez
M.I.
,
Lopes
F.
,
McKay
D.M.
and
Reyes
J.L.
(
2018
)
Mast cell deficiency in mice results in biomass overgrowth and delayed expulsion of the rat tapeworm Hymenolepis diminuta
.
Biosci. Rep.
25.
McKay
D.M.
(
2010
)
The immune response to and immunomodulation by Hymenolepis diminuta
.
Parasitology
137
,
385
394
[PubMed]
26.
Galli
S.J.
,
Tsai
M.
,
Marichal
T.
,
Tchougounova
E.
,
Reber
L.L.
and
Pejler
G.
(
2015
)
Approaches for analyzing the roles of mast cells and their proteases in vivo
.
Adv. Immunol.
126
,
45
127
[PubMed]
27.
Ishih
A.
,
Nishimura
M.
and
Sano
M.
(
1992
)
Differential establishment and survival of Hymenolepis diminuta in syngeneic and outbred rat strains
.
J. Helminthol.
66
,
132
136
[PubMed]
28.
Graepel
R.
,
Leung
G.
,
Wang
A.
,
Villemaire
M.
,
Jirik
F.R.
,
Sharkey
K.A.
et al.
(
2013
)
Murine autoimmune arthritis is exaggerated by infection with the rat tapeworm, Hymenolepis diminuta
.
Int. J. Parasitol.
43
,
593
601
[PubMed]
29.
Hepworth
M.R.
,
Maurer
M.
and
Hartmann
S.
(
2012
)
Regulation of type 2 immunity to helminths by mast cells
.
Gut microbes
3
,
476
481
[PubMed]
30.
Silva
da
,
Z.
E.
,
Jamur
M.C.
and
Oliver
C.
(
2014
)
Mast cell function: a new vision of an old cell
.
J. Histochem. Cytochem.: Off. J. Histochem. Soc.
62
,
698
738
31.
Arizono
N.
,
Kasugai
T.
,
Yamada
M.
,
Okada
M.
,
Morimoto
M.
,
Tei
H.
et al.
(
1993
)
Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats
.
Blood
81
,
2572
2578
[PubMed]
32.
Alizadeh
H.
and
Murrell
K.D.
(
1984
)
The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice
.
J. Parasitol.
70
,
767
773
[PubMed]
33.
Divekar
R.
and
Kita
H.
(
2015
)
Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation
.
Curr. Opin. Allergy Clin. Immunol.
15
,
98
103
[PubMed]
34.
Wang
W.
,
Li
Y.
,
Lv
Z.
,
Chen
Y.
,
Li
Y.
,
Huang
K.
et al.
(
2018
)
Bronchial allergen challenge of patients with atopic asthma triggers an alarmin (IL-33, TSLP, and IL-25) response in the airways epithelium and submucosa
.
J. Immunol.
201
,
2221
2231
35.
Oyesola
O.O.
,
Fruh
S.P.
,
Webb
L.M.
and
Tait Wojno
E.D.
(
2018
)
Cytokines and beyond: Regulation of innate immune responses during helminth infection
.
Cytokine
[PubMed]
36.
Hirata
M.
,
Hara
T.
,
Kage
M.
,
Fukuma
T.
and
Sendo
F.
(
2002
)
Neutropenia augments experimentally induced Schistosoma japonicum egg granuloma formation in CBA mice, but not in C57BL/6 mice
.
Parasite Immunol.
24
,
479
488
[PubMed]
37.
Pesce
J.T.
,
Liu
Z.
,
Hamed
H.
,
Alem
F.
,
Whitmire
J.
,
Lin
H.
et al.
(
2008
)
Neutrophils clear bacteria associated with parasitic nematodes augmenting the development of an effective Th2-type response
.
J. Immunol.
180
,
464
474
38.
Morampudi
V.
,
Bhinder
G.
,
Wu
X.
,
Dai
C.
,
Sham
H.P.
,
Vallance
B.A.
et al.
(
2014
)
DNBS/TNBS colitis models: providing insights into inflammatory bowel disease and effects of dietary fat
.
J. Visual. Exp.: JoVE
e51297
39.
Reyes
J.L.
,
Fernando
M.R.
,
Lopes
F.
,
Leung
G.
,
Mancini
N.L.
,
Matisz
C.E.
et al.
(
2016
)
IL-22 restrains tapeworm-mediated protection against experimental colitis via regulation of IL-25 expression
.
PLoS Pathog.
12
,
e1005481
[PubMed]
40.
Callejas
B.E.
,
Martinez Saucedo
D.
and
Terrazas
L.I.
(
2018
)
Parasites as negative regulators of cancer
.
Biosci. Rep.
[PubMed]
41.
Logan
J.
,
Navarro
S.
,
Loukas
A.
and
Giacomin
P.
(
2018
)
Helminth-induced regulatory T cells and suppression of allergic responses
.
Curr. Opin. Immunol.
54
,
1
6
[PubMed]
42.
Blank
M.
,
Bashi
T.
,
Lachnish
J.
,
Ben-Ami-Shor
D.
,
Shovman
O.
,
Fridkin
M.
et al.
(
2018
)
Helminths-based bi-functional molecule, tuftsin-phosphorylcholine (TPC), ameliorates an established murine arthritis
.
PLoS One
13
,
e0200615
[PubMed]
43.
McLauchlan
P.E.
,
Roberts
H.C.
,
Loxton
N.J.
,
Wastling
J.M.
,
Newlands
G.F.
and
Chappell
L.H.
(
1999
)
Mucosal mast cell responses and release of mast cell protease-I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A
.
Parasite Immunol.
21
,
151
161
[PubMed]
44.
Hunter
M.M.
,
Wang
A.
,
Hirota
C.L.
and
McKay
D.M.
(
2005
)
Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis
.
J. Immunol.
174
,
7368
7375
45.
Matisz
C.E.
,
Leung
G.
,
Reyes
J.L.
,
Wang
A.
,
Sharkey
K.A.
and
McKay
D.M.
(
2015
)
Adoptive transfer of helminth antigen-pulsed dendritic cells protects against the development of experimental colitis in mice
.
Eur. J. Immunol.
45
,
3126
3139
[PubMed]
46.
Reyes
J.L.
,
Lopes
F.
,
Leung
G.
,
Mancini
N.L.
,
Matisz
C.E.
,
Wang
A.
et al.
(
2016
)
Treatment with cestode parasite antigens results in recruitment of CCR2+ myeloid cells, the adoptive transfer of which ameliorates colitis
.
Infect. Immun.
84
,
3471
3483
[PubMed]
47.
Hunter
M.M.
,
Wang
A.
,
Parhar
K.S.
,
Johnston
M.J.
,
Van Rooijen
N.
,
Beck
P.L.
et al.
(
2010
)
In vitro-derived alternatively activated macrophages reduce colonic inflammation in mice
.
Gastroenterology
138
,
1395
1405
[PubMed]
48.
Liu
J.
,
Morey
R.A.
,
Wilson
J.K.
and
Parker
W.
(
2017
)
Practices and outcomes of self-treatment with helminths based on physicians’ observations
.
J. Helminthol.
91
,
267
277
[PubMed]
49.
Shi
M.
,
Wang
A.
,
Prescott
D.
,
Waterhouse
C.C.
,
Zhang
S.
,
McDougall
J.J.
et al.
(
2011
)
Infection with an intestinal helminth parasite reduces Freund’s complete adjuvant-induced monoarthritis in mice
.
Arthritis Rheum.
63
,
434
444
[PubMed]
50.
Leonardi
I.
,
Gerstgrasser
A.
,
Schmidt
T. S.B.
,
Nicholls
F.
,
Tewes
B.
,
Greinwald
R.
et al.
(
2017
)
Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
.
Sci. Rep.
7
,
16500
[PubMed]
51.
Hansen
C.S.
,
Hasseldam
H.
,
Bacher
I.H.
,
Thamsborg
S.M.
,
Johansen
F.F.
and
Kringel
H.
(
2017
)
Trichuris suis secrete products that reduce disease severity in a multiple sclerosis model
.
Acta. Parasitol.
62
,
22
28
[PubMed]
52.
Ebner
F.
,
Hepworth
M.R.
,
Rausch
S.
,
Janek
K.
,
Niewienda
A.
,
Kuhl
A.
et al.
(
2014
)
Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease
.
Allergy
69
,
1489
1497
[PubMed]
53.
Summers
R.W.
,
Elliott
D.E.
,
Urban
J.F.
Jr
,
Thompson
R.A.
and
Weinstock
J.V.
(
2005
)
Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial
.
Gastroenterology
128
,
825
832
[PubMed]
54.
Summers
R.W.
,
Elliott
D.E.
,
Qadir
K.
,
Urban
J.F.
Jr
,
Thompson
R.
and
Weinstock
J.V.
(
2003
)
Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease
.
Am. J. Gastroenterol.
98
,
2034
2041
[PubMed]
55.
Sandborn
W.J.
,
Elliott
D.E.
,
Weinstock
J.
,
Summers
R.W.
,
Landry-Wheeler
A.
,
Silver
N.
et al.
(
2013
)
Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn’s disease
.
Aliment. Pharmacol. Ther.
38
,
255
263
56.
Summers
R.W.
,
Elliott
D.E.
,
Urban
J.F.
Jr
,
Thompson
R.
and
Weinstock
J.V.
(
2005
)
Trichuris suis therapy in Crohn’s disease
.
Gut
54
,
87
90
[PubMed]
57.
Fleming
J.O.
,
Isaak
A.
,
Lee
J.E.
,
Luzzio
C.C.
,
Carrithers
M.D.
,
Cook
T.D.
et al.
(
2011
)
Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study
.
Multiple Sclerosis
17
,
743
754
[PubMed]
58.
Bager
P.
,
Arnved
J.
,
Ronborg
S.
,
Wohlfahrt
J.
,
Poulsen
L.K.
,
Westergaard
T.
et al.
(
2010
)
Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial
.
J. Allergy Clin. Immunol.
125
,
123-130 e121-123
[PubMed]
59.
Trichuris Suis Ova in Peanut and Tree Nut Allergy. ed.), https://ClinicalTrials.gov/show/NCT01070498
60.
Safety and Effectiveness of CNDO 201Trichuris Suis Ova (TSO) for the Treatment of Moderate to Severe Plaque Psoriasis. ed.), https://ClinicalTrials.gov/show/NCT01836939
61.
Trichuris Suis Ova in Autism Spectrum Disorders. ed.)∧eds.), https://ClinicalTrials.gov/show/NCT01040221
62.
Croese
J.
,
O’Neil
J.
,
Masson
J.
,
Cooke
S.
,
Melrose
W.
,
Pritchard
D.
et al.
(
2006
)
A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors
.
Gut
55
,
136
137
[PubMed]
63.
Daveson
A.J.
,
Jones
D.M.
,
Gaze
S.
,
McSorley
H.
,
Clouston
A.
,
Pascoe
A.
et al.
(
2011
)
Effect of hookworm infection on wheat challenge in celiac disease–a randomised double-blinded placebo controlled trial
.
PLoS One
6
,
e17366
[PubMed]
64.
Feary
J.R.
,
Venn
A.J.
,
Mortimer
K.
,
Brown
A.P.
,
Hooi
D.
,
Falcone
F.H.
et al.
(
2010
)
Experimental hookworm infection: a randomized placebo-controlled trial in asthma
.
Clin. Exp. Allergy: J. Br. Soc. Allergy Clin. Immunol.
40
,
299
306
65.
Feary
J.
,
Venn
A.
,
Brown
A.
,
Hooi
D.
,
Falcone
F.H.
,
Mortimer
K.
et al.
(
2009
)
Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study
.
Clin. Exp. Allergy: J. Br. Soc. Allergy Clin. Immunol.
39
,
1060
1068
66.
Mortimer
K.
,
Brown
A.
,
Feary
J.
,
Jagger
C.
,
Lewis
S.
,
Antoniak
M.
et al.
(
2006
)
Dose-ranging study for trials of therapeutic infection with Necator americanus in humans
.
Am. J. Trop. Med. Hyg.
75
,
914
920
[PubMed]
67.
Worms for Immune Regulation of Multiple Sclerosis. ed.), https://ClinicalTrials.gov/show/NCT01470521
68.
Blount
D.
,
Hooi
D.
,
Feary
J.
,
Venn
A.
,
Telford
G.
,
Brown
A.
et al.
(
2009
)
Immunologic profiles of persons recruited for a randomized, placebo-controlled clinical trial of hookworm infection
.
Am. J. Trop. Med. Hyg.
81
,
911
916
[PubMed]
69.
Broadhurst
M.J.
,
Leung
J.M.
,
Kashyap
V.
,
McCune
J.M.
,
Mahadevan
U.
,
McKerrow
J.H.
et al.
(
2010
)
IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient
.
Sci. Transl. Med.
2
,
60ra88
[PubMed]
70.
van den Biggelaar
A.H.
,
Rodrigues
L.C.
,
van Ree
R.
,
van der Zee
J.S.
,
Hoeksma-Kruize
Y.C.
,
Souverijn
J.H.
et al.
(
2004
)
Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren
.
J. Infect. Dis.
189
,
892
900
[PubMed]
71.
Fleming
J.O.
and
Cook
T.D.
(
2006
)
Multiple sclerosis and the hygiene hypothesis
.
Neurology
67
,
2085
2086
[PubMed]
72.
Ganley-Leal
L.M.
,
Mwinzi
P.N.
,
Cetre-Sossah
C.B.
,
Andove
J.
,
Hightower
A.W.
,
Karanja
D.M.
et al.
(
2006
)
Higher percentages of circulating mast cell precursors correlate with susceptibility to reinfection with Schistosoma mansoni
.
Am. J. Trop. Med. Hyg.
75
,
1053
1057
[PubMed]
73.
Prendergast
C.T.
,
Sanin
D.E.
and
Mountford
A.P.
(
2016
)
CD4 T-cell hyporesponsiveness induced by schistosome larvae is not dependent upon eosinophils but may involve connective tissue mast cells
.
Parasite Immunol.
38
,
81
92
[PubMed]
74.
Ford
M.J.
,
Bickle
Q.D.
and
Taylor
M.G.
(
1987
)
Immunity to Schistosoma mansoni in congenitally athymic, irradiated and mast cell-depleted rats
.
Parasitology
94
,
313
326
[PubMed]
75.
Sher
A.
,
Correa-Oliveira
R.
,
Hieny
S.
and
Hussain
R.
(
1983
)
Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. IV. Analysis of the role of IgE antibodies and mast cells
.
J. Immunol.
131
,
1460
1465
[PubMed]
76.
Sewell
D.
,
Qing
Z.
,
Reinke
E.
,
Elliot
D.
,
Weinstock
J.
,
Sandor
M.
et al.
(
2003
)
Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization
.
Int. Immunol.
15
,
59
69
[PubMed]
77.
Flamme
La
,
C.
A.
,
Ruddenklau
K.
and
Backstrom
B.T.
(
2003
)
Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis
.
Infect. Immun.
71
,
4996
5004
[PubMed]
78.
Cooke
A.
,
Tonks
P.
,
Jones
F.M.
,
O’Shea
H.
,
Hutchings
P.
,
Fulford
A.J.
et al.
(
1999
)
Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice
.
Parasite Immunol.
21
,
169
176
[PubMed]
79.
Zaccone
P.
,
Fehervari
Z.
,
Jones
F.M.
,
Sidobre
S.
,
Kronenberg
M.
,
Dunne
D.W.
et al.
(
2003
)
Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes
.
Eur. J. Immunol.
33
,
1439
1449
[PubMed]
80.
Elliott
D.E.
,
Li
J.
,
Blum
A.
,
Metwali
A.
,
Qadir
K.
,
Urban
J.F.
Jr
et al.
(
2003
)
Exposure to schistosome eggs protects mice from TNBS-induced colitis
.
Am. J. Physiol. Gastrointest. Liver Physiol.
284
,
G385
G391
81.
Smith
P.
,
Mangan
N.E.
,
Walsh
C.M.
,
Fallon
R.E.
,
McKenzie
A.N.
,
van Rooijen
N.
et al.
(
2007
)
Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism
.
J. Immunol.
178
,
4557
4566
82.
Moreels
T.G.
,
Nieuwendijk
R.J.
,
De Man
J.G.
,
De Winter
B.Y.
,
Herman
A.G.
,
Van Marck
E.A.
et al.
(
2004
)
Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats
.
Gut
53
,
99
107
[PubMed]
83.
Mangan
N.E.
,
van Rooijen
N.
,
McKenzie
A.N.
and
Fallon
P.G.
(
2006
)
Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness
.
J. Immunol.
176
,
138
147
84.
Smits
H.H.
,
Hammad
H.
,
van Nimwegen
M.
,
Soullie
T.
,
Willart
M.A.
,
Lievers
E.
et al.
(
2007
)
Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection
.
J. Allergy Clin. Immunol.
120
,
932
940
[PubMed]
85.
Mangan
N.E.
,
Fallon
R.E.
,
Smith
P.
,
van Rooijen
N.
,
McKenzie
A.N.
and
Fallon
P.G.
(
2004
)
Helminth infection protects mice from anaphylaxis via IL-10-producing B cells
.
J. Immunol.
173
,
6346
6356
86.
Nagayama
Y.
,
Watanabe
K.
,
Niwa
M.
,
McLachlan
S.M.
and
Rapoport
B.
(
2004
)
Schistosoma mansoni and alpha-galactosylceramide: prophylactic effect of Th1 Immune suppression in a mouse model of Graves’ hyperthyroidism
.
J. Immunol.
173
,
2167
2173
87.
Osada
Y.
,
Shimizu
S.
,
Kumagai
T.
,
Yamada
S.
and
Kanazawa
T.
(
2009
)
Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators
.
Int. J. Parasitol.
39
,
457
464
[PubMed]
88.
Angkasekwinai
P.
,
Sodthawon
W.
,
Jeerawattanawart
S.
,
Hansakon
A.
,
Pattanapanyasat
K.
and
Wang
Y.H.
(
2017
)
ILC2s activated by IL-25 promote antigen-specific Th2 and Th9 functions that contribute to the control of Trichinella spiralis infection
.
PLoS One
12
,
e0184684
[PubMed]
89.
Ding
J.
,
Bai
X.
,
Wang
X.
,
Shi
H.
,
Cai
X.
,
Luo
X.
et al.
(
2017
)
Immune Cell Responses and Cytokine Profile in Intestines of Mice Infected with Trichinella spiralis
.
Front. Microbiol.
8
,
2069
[PubMed]
90.
Gruden-Movsesijan
A.
,
Ilic
N.
,
Mostarica-Stojkovic
M.
,
Stosic-Grujicic
S.
,
Milic
M.
and
Sofronic-Milosavljevic
L.
(
2008
)
Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats
.
Exp. Parasitol.
118
,
641
647
[PubMed]
91.
Gruden-Movsesijan
A.
,
Ilic
N.
,
Mostarica-Stojkovic
M.
,
Stosic-Grujicic
S.
,
Milic
M.
and
Sofronic-Milosavljevic
L.
(
2010
)
Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats
.
Parasite Immunol.
32
,
450
459
[PubMed]
92.
Sofronic-Milosavljevic
L.J.
,
Radovic
I.
,
Ilic
N.
,
Majstorovic
I.
,
Cvetkovic
J.
and
Gruden-Movsesijan
A.
(
2013
)
Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis
.
Med. Microbiol. Immunol.
202
,
239
249
93.
Saunders
K.A.
,
Raine
T.
,
Cooke
A.
and
Lawrence
C.E.
(
2007
)
Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection
.
Infect. Immun.
75
,
397
407
[PubMed]
94.
Khan
W.I.
,
Blennerhasset
P.A.
,
Varghese
A.K.
,
Chowdhury
S.K.
,
Omsted
P.
,
Deng
Y.
et al.
(
2002
)
Intestinal nematode infection ameliorates experimental colitis in mice
.
Infect. Immun.
70
,
5931
5937
[PubMed]
95.
Motomura
Y.
,
Wang
H.
,
Deng
Y.
,
El-Sharkawy
R.T.
,
Verdu
E.F.
and
Khan
W.I.
(
2009
)
Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis
.
Clin. Exp. Immunol.
155
,
88
95
[PubMed]
96.
Ashour
D.S.
,
Othman
A.A.
,
Shareef
M.M.
,
Gaballah
H.H.
and
Mayah
W.W.
(
2014
)
Interactions between Trichinella spiralis infection and induced colitis in mice
.
J. Helminthol.
88
,
210
218
[PubMed]
97.
Du
L.
,
Wei
H.
,
Li
L.
,
Shan
H.
,
Yu
Y.
,
Wang
Y.
et al.
(
2014
)
Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Ralpha in vitro
.
Cell. Immunol.
288
,
1
7
[PubMed]
98.
Shimokawa
C.
,
Kanaya
T.
,
Hachisuka
M.
,
Ishiwata
K.
,
Hisaeda
H.
,
Kurashima
Y.
et al.
(
2017
)
Mast cells are crucial for induction of group 2 innate lymphoid cells and clearance of helminth infections
.
Immunity
46
,
863–874 e864
[PubMed]
99.
Hashimoto
K.
,
Uchikawa
R.
,
Tegoshi
T.
,
Takeda
K.
,
Yamada
M.
and
Arizono
N.
(
2010
)
Immunity-mediated regulation of fecundity in the nematode Heligmosomoides polygyrus–the potential role of mast cells
.
Parasitology
137
,
881
887
[PubMed]
100.
Wilson
M.S.
,
Taylor
M.D.
,
O’Gorman
M.T.
,
Balic
A.
,
Barr
T.A.
,
Filbey
K.
et al.
(
2010
)
Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation
.
Eur. J. Immunol.
40
,
1682
1696
[PubMed]
101.
Elliott
D.E.
,
Setiawan
T.
,
Metwali
A.
,
Blum
A.
,
Urban
J.F.
Jr
and
Weinstock
J.V.
(
2004
)
Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice
.
Eur. J. Immunol.
34
,
2690
2698
[PubMed]
102.
Hang
L.
,
Setiawan
T.
,
Blum
A.M.
,
Urban
J.
,
Stoyanoff
K.
,
Arihiro
S.
et al.
(
2010
)
Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity
.
J. Immunol.
185
,
3184
3189
103.
Hang
L.
,
Blum
A.M.
,
Setiawan
T.
,
Urban
J.F.
Jr
,
Stoyanoff
K.M.
and
Weinstock
J.V.
(
2013
)
Heligmosomoides polygyrus bakeri infection activates colonic Foxp3+ T cells enhancing their capacity to prevent colitis
.
J. Immunol.
191
,
1927
1934
104.
Wilson
M.S.
,
Taylor
M.D.
,
Balic
A.
,
Finney
C.A.
,
Lamb
J.R.
and
Maizels
R.M.
(
2005
)
Suppression of allergic airway inflammation by helminth-induced regulatory T cells
.
J. Exp. Med.
202
,
1199
1212
[PubMed]
105.
Kitagaki
K.
,
Businga
T.R.
,
Racila
D.
,
Elliott
D.E.
,
Weinstock
J.V.
and
Kline
J.N.
(
2006
)
Intestinal helminths protect in a murine model of asthma
.
J. Immunol.
177
,
1628
1635
106.
Salinas-Carmona
M.C.
,
de la Cruz-Galicia
G.
,
Perez-Rivera
I.
,
Solis-Soto
J.M.
,
Segoviano-Ramirez
J.C.
,
Vazquez
A.V.
et al.
(
2009
)
Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections
.
Autoimmunity
42
,
25
32
[PubMed]
107.
Bashir
M.E.
,
Andersen
P.
,
Fuss
I.J.
,
Shi
H.N.
and
Nagler-Anderson
C.
(
2002
)
An enteric helminth infection protects against an allergic response to dietary antigen
.
J. Immunol.
169
,
3284
3292
108.
Sutton
T.L.
,
Zhao
A.
,
Madden
K.B.
,
Elfrey
J.E.
,
Tuft
B.A.
,
Sullivan
C.A.
et al.
(
2008
)
Anti-Inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model
.
Infect. Immun.
76
,
4772
4782
[PubMed]
109.
Setiawan
T.
,
Metwali
A.
,
Blum
A.M.
,
Ince
M.N.
,
Urban
J.F.
Jr
,
Elliott
D.E.
et al.
(
2007
)
Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine
.
Infect. Immun.
75
,
4655
4663
[PubMed]
110.
Wakelin
D.
,
Goyal
P.K.
,
Dehlawi
M.S.
and
Hermanek
J.
(
1994
)
Immune responses to Trichinella spiralis and T. pseudospiralis in mice
.
Immunology
81
,
475
479
[PubMed]
111.
Wu
Z.
,
Nagano
I.
,
Asano
K.
and
Takahashi
Y.
(
2010
)
Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response
.
Parasitol. Res.
107
,
1173
1188
[PubMed]
112.
Sato
H.
,
Kamiya
H.
,
Oku
Y.
and
Kamiya
M.
(
1994
)
Infection course of the strobilar stage of Taenia crassiceps in golden hamsters, with reference to host responses
.
Parasitol. Res.
80
,
99
103
[PubMed]
113.
Espinoza-Jimenez
A.
,
Rivera-Montoya
I.
,
Cardenas-Arreola
R.
,
Moran
L.
and
Terrazas
L.I.
(
2010
)
Taenia crassiceps infection attenuates multiple low-dose streptozotocin-induced diabetes
.
J. Biomed. Biotechnol.
2010
,
850541
[PubMed]
114.
Reyes
J.L.
,
Espinoza-Jiménez
A.F.
,
González
M.I.
,
Verdin
L.
and
Terrazas
L.I.
(
2011
)
Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis
.
Cell. Immunol.
267
,
77
87
[PubMed]
115.
Ledesma-Soto
Y.
,
Callejas
B.E.
,
Terrazas
C.A.
,
Reyes
J.L.
,
Espinoza-Jimenez
A.
,
Gonzalez
M.I.
et al.
(
2015
)
Extraintestinal helminth infection limits pathology and proinflammatory cytokine expression during DSS-induced ulcerative colitis: a role for alternatively activated macrophages and prostaglandins
.
BioMed Res. Int.
2015
,
563425
[PubMed]
116.
Specht
S.
,
Frank
J.K.
,
Alferink
J.
,
Dubben
B.
,
Layland
L.E.
,
Denece
G.
et al.
(
2011
)
CCL17 controls mast cells for the defense against filarial larval entry
.
J. Immunol.
186
,
4845
4852
117.
Muhsin
M.
,
Ajendra
J.
,
Gentil
K.
,
Berbudi
A.
,
Neumann
A.L.
,
Klaas
L.
et al.
(
2018
)
IL-6 is required for protective immune responses against early filarial infection
.
Int. J. Parasitol.
48
,
925
935
[PubMed]
118.
Hubner
M.P.
,
Stocker
J.T.
and
Mitre
E.
(
2009
)
Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells
.
Immunology
127
,
512
522
[PubMed]
119.
Ajendra
J.
,
Berbudi
A.
,
Hoerauf
A.
and
Hubner
M.P.
(
2016
)
Combination of worm antigen and proinsulin prevents type 1 diabetes in NOD mice after the onset of insulitis
.
Clin. Immunol.
164
,
119
122
120.
Dittrich
A.M.
,
Erbacher
A.
,
Specht
S.
,
Diesner
F.
,
Krokowski
M.
,
Avagyan
A.
et al.
(
2008
)
Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model
.
J. Immunol.
180
,
1792
1799
121.
Berbudi
A.
,
Surendar
J.
,
Ajendra
J.
,
Gondorf
F.
,
Schmidt
D.
,
Neumann
A.L.
et al.
(
2016
)
Filarial infection or antigen administration improves glucose tolerance in diet-induced obese mice
.
J. Innate Immun.
8
,
601
616
[PubMed]
122.
Yang
Y.
,
Xiao
S.
,
Ren
H.
,
Wu
J.
,
Feng
Z.
and
Hotez
P.J.
(
1999
)
Cutaneous and subcutaneous mast cell and eosinophil responses after challenge in mice vaccinated with living infective third-stage hookworm larvae
.
Chin. Med. J.
112
,
1020
1023
[PubMed]
123.
Ferreira
I.
,
Smyth
D.
,
Gaze
S.
,
Aziz
A.
,
Giacomin
P.
,
Ruyssers
N.
et al.
(
2013
)
Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis
.
Infect. Immun.
81
,
2104
2111
[PubMed]
124.
Matsumoto
M.
,
Sasaki
Y.
,
Yasuda
K.
,
Takai
T.
,
Muramatsu
M.
,
Yoshimoto
T.
et al.
(
2013
)
IgG and IgE collaboratively accelerate expulsion of Strongyloides venezuelensis in a primary infection
.
Infect. Immun.
81
,
2518
2527
[PubMed]
125.
Mukai
K.
,
Karasuyama
H.
,
Kabashima
K.
,
Kubo
M.
and
Galli
S.J.
(
2017
)
Differences in the importance of mast cells, basophils, IgE, and IgG versus that of CD4(+) T cells and ILC2 cells in primary and secondary immunity to strongyloides venezuelensis
.
Infect. Immun.
85
,
[PubMed]
126.
Peres
R.S.
,
Chiuso-Minicucci
F.
,
da Rosa
L.C.
,
Domingues
A.
,
Zorzella-Pezavento
S.F.
,
Franca
T.G.
et al.
(
2013
)
Previous contact with Strongyloides venezuelensis contributed to prevent insulitis in MLD-STZ diabetes
.
Exp. Parasitol.
134
,
183
189
[PubMed]
127.
Mitchell
L.A.
,
Wescott
R.B.
and
Perryman
L.E.
(
1983
)
Kinetics of expulsion of the nematode, Nippostrongylus brasiliensis, in mast-cell deficient W/WV mice
.
Parasite Immunol.
5
,
1
12
[PubMed]
128.
Wohlleben
G.
,
Trujillo
C.
,
Muller
J.
,
Ritze
Y.
,
Grunewald
S.
,
Tatsch
U.
et al.
(
2004
)
Helminth infection modulates the development of allergen-induced airway inflammation
.
Int. Immunol.
16
,
585
596
[PubMed]
129.
Mo
H.M.
,
Lei
J.H.
,
Jiang
Z.W.
,
Wang
C.Z.
,
Cheng
Y.L.
,
Li
Y.L.
et al.
(
2008
)
Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice
.
Parasitol. Res.
103
,
1183
1189
[PubMed]
130.
Yang
J.
,
Zhao
J.
,
Yang
Y.
,
Zhang
L.
,
Yang
X.
,
Zhu
X.
et al.
(
2007
)
Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma
.
Immunology
120
,
8
18
[PubMed]
131.
Mo
H.M.
,
Liu
W.Q.
,
Lei
J.H.
,
Cheng
Y.L.
,
Wang
C.Z.
and
Li
Y.L.
(
2007
)
Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice
.
Exp. Parasitol.
116
,
385
389
[PubMed]
132.
Zheng
X.
,
Hu
X.
,
Zhou
G.
,
Lu
Z.
,
Qiu
W.
,
Bao
J.
et al.
(
2008
)
Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response
.
J. Neuroimmunol.
194
,
107
114
[PubMed]
133.
Sorobetea
D.
,
Holm
J.B.
,
Henningsson
H.
,
Kristiansen
K.
and
Svensson-Frej
M.
(
2017
)
Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity
.
Eur. J. Immunol.
47
,
257
268
[PubMed]
134.
Betts
C.J.
and
Else
K.J.
(
1999
)
Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not critical in resistance to Trichuris muris
.
Parasite Immunol.
21
,
45
52
[PubMed]
135.
Koyama
K.
and
Ito
Y.
(
2000
)
Mucosal mast cell responses are not required for protection against infection with the murine nematode parasite Trichuris muris
.
Parasite Immunol.
22
,
13
20
[PubMed]
136.
Vegas-Sanchez
M.C.
,
Rollan-Landeras
E.
,
Garcia-Rodriguez
J.J.
and
Bolas-Fernandez
F.
(
2015
)
Induction of ulcerative colitis in mice influences the course of infection with the nematode Trichuris muris
.
J. Helminthol.
89
,
593
600
[PubMed]
137.
Chenery
A.L.
,
Antignano
F.
,
Burrows
K.
,
Scheer
S.
,
Perona-Wright
G.
and
Zaph
C.
(
2016
)
Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation
.
Infect. Immun.
84
,
491
501
[PubMed]
This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).