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.
Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae
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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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