The Roles of MyD88 in the Development of Protective Immunity and Pathology During Chlamydial Urogenital Infection in Mice

Abstract:

C57BL/6J WT and mice deficient in MyD88 (MyD88 KO) were inoculated intravaginally with 1 × 104 IFUs of live C. muridarum organisms. Half mice of each group were reinfected on day 54 after primary infection. Vaginal swabs were taken every 3 or 4 days to monitor live organism shedding. On day 80 after the primary infection, mice were sacrificed, and the vaginal tract was isolated for pathology. The spleen cells were collected and IL-4, IL-5, IL-17 and IFN-γ were detected by ELISA in the spleen cells culture supernatant after restimulated by MoPn EB. The titers of different Ab isotypes were measured in mice serum by Indirect Immunofluorescence Assay. The Chlamydia shedding time of MyD88 KO mice was similar to WT. Not only the gross appearance of the isolated genital tracts, but also the dilation and inflammation scores under microscope showed that the genital tract pathology from the MyD88-deficient mice was much more severe than WT after primary infection. The results of Th2 (IL-4 & IL-5), Th1 (IFN-γ) and Th17 (IL-17) cytokines from the in vitro restimulated splenocyte culture supernatant showed that MyD88 deficient mice produced significantly lower levels of IFN-γ and IL-17 but much higher levels of IL-4 and IL-5 than WT mice either after the primary infection or reinfection with Chlamydia. There were no significant differences in Ab isotype levels between the two tested groups. However, the ratio of MoPn specific serum IgG2a/IgG1 in MyD88-deficient mice was less than 1 and significantly lower than that in WT mice. MyD88 is dispensable for protective immunity but required for inflammatory pathologies.