Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae.
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-gamma (interferon-gamma)/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-gamma 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.
Chen
Shyi-Jou
SJ
The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Chu
Mong-Ling
ML
Wang
Chia-Jen
CJ
Liao
Ching-Len
CL
Hsieh
Shie-Liang
SL
Sytwu
Huey-Kang
HK
Wang
Chih-Chien
CC
D000208:Acute Disease; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001921:Brain / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006193:Haemophilus influenzae / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008583:Meningitis, Haemophilus / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012720:Severity of Illness Index; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000942:Antigens, Bacterial; D016207:Cytokines