Innate IFNγ is essential for systemic Chlamydia control while CD4 T cell-dependent IFNγ production is highly redundant in the female reproductive tract
Protective immunity to the obligate intracellular bacterium Chlamydia is thought to rely on CD4 T cell-dependent IFN{gamma} production. Nevertheless, whether IFN{gamma} is produced by other cellular source during Chlamydia infection and how CD4 T cell-dependent and -independent IFN{gamma} contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFN{gamma} produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal inoculation, IFN{gamma}-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFN{gamma} and CD4 T cells in host defense against Chlamydia. In Rag-deficient mice, IFN{gamma} produced by innate lymphocytes (ILCs) accounted for early bacterial containment and prolonged survival in the absence of adaptive immunity. Although group I ILCs are potent IFN{gamma} producers, we found that mature NK cells and ILC1 were not the sole source for innate IFN{gamma} in response to Chlamydia. T cell adoptive transfer experiments revealed that WT and IFN{gamma}-deficient CD4 T cells were equally capable of mediating effective bacterial killing in the FRT during the early stage of Chlamydia infection. Together, our results revealed that innate IFN{gamma} is essential for preventing systemic Chlamydia dissemination, whereas IFN{gamma} produced by CD4 T cells is largely dispensable at the FRT mucosa.