Mice deficient in MyD88 Develop a Th2-dominant response and severe pathology in the upper genital tract following Chlamydia muridarum infection.
MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms.
Chen
Lili
L
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Lei
Lei
L
Chang
Xiaotong
X
Li
Zhihong
Z
Lu
Chunxue
C
Zhang
Xiaoyun
X
Wu
Yimou
Y
Yeh
I-Tien
IT
Zhong
Guangming
G
D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000276:immunology* / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency* / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014566:Urogenital System / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D014621:Vagina / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
D020381:Interleukin-17; D053582:Interleukin-1alpha; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha