To investigate the kinetic Th1/Th2 immunopathogenic mechanisms of Haemophilus influenzae meningitis, we established a murine experimental model of meningitis and elucidated the Th1/Th2 immune responses in T1/T2 doubly transgenic mice based on a BALB/c background under the control of the IFN-γ (interferon-γ)/IL-4 (interleukin-4) promoters respectively. NTHi (non-typeable Haemophilus influenzae) meningitis was induced in these mice by inoculation with either a colonized (CNTHi) or invasive (INTHi) strain of NTHi. Mice inoculated with CNTHi displayed a less severe degree of disease in terms of clinical symptoms, mortality rate and brain histopathology. Conversely, INTHi-inoculated mice had more severe clinical symptoms. CNTHi-inoculated mice had a more significant Th1 response in terms of a higher percentage and longer maintenance of Th1 cells, and more production of IFN-γ from strain-specific antigen-stimulated splenocytes than INTHi-inoculated mice. In contrast, INTHi-inoculated mice had a more significant Th2 response. This was due to a significant increase in IL-4-producing CD4+ T-cells (Th2 cells) and more production of IL-4 from strain-specific antigen-stimulated splenocytes accompanied by a rapid decline of Th1 cells in INTHi-inoculated mice. In conclusion, the preferential Th1/Th2 trend in this murine model of NTHi meningitis is correlated with clinical severity as well as isolated characteristics of the pathogens themselves.
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October 2006
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Research Article|
September 13 2006
Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae
Shyi-Jou Chen;
Shyi-Jou Chen
*The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
†Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Mong-Ling Chu;
Mong-Ling Chu
†Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Chia-Jen Wang;
Chia-Jen Wang
‡Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
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Ching-Len Liao;
Ching-Len Liao
§Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
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Shie-Liang Hsieh;
Shie-Liang Hsieh
∥Department of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Huey-Kang Sytwu;
*The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
‡Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
§Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
Correspondence: Professor Chih-Chien Wang (email [email protected]) or Professor Huey-Kang Sytwu (email [email protected]).
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Chih-Chien Wang
†Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Correspondence: Professor Chih-Chien Wang (email [email protected]) or Professor Huey-Kang Sytwu (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 15 2006
Accepted:
April 20 2006
Accepted Manuscript online:
April 20 2006
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 111 (4): 253–263.
Article history
Received:
March 15 2006
Accepted:
April 20 2006
Accepted Manuscript online:
April 20 2006
Citation
Shyi-Jou Chen, Mong-Ling Chu, Chia-Jen Wang, Ching-Len Liao, Shie-Liang Hsieh, Huey-Kang Sytwu, Chih-Chien Wang; Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae. Clin Sci (Lond) 1 October 2006; 111 (4): 253–263. doi: https://doi.org/10.1042/CS20060060
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