Gann, J. I. | bioRxiv Science

bioRxiv2022

IFNγ and antibody synergize to enhance protective immunity against Chlamydia dissemination and female reproductive tract reinfections

CD4 T cell-dependent IFN{gamma} production and antibody are the two best known effectors for protective immunity against Chlamydia female reproductive tract (FRT) infection. Nevertheless, mice lacking either IFN{gamma} or B cells are capable of clearing vast majority of Chlamydia from the female reproductive tract (FRT), while suffering from varying degrees of disseminated infection. In this study, we investigated whether IFN{gamma} and B cells play complimentary roles in host defense against Chlamydia and evaluated their relative contributions in systemic and mucosal tissues. Using mice deficient in both IFN{gamma} and B cells (IFN{gamma}-/- x {micro}MT), we showed that mice lacking both effectors are highly susceptible to lethal systemic Chlamydia dissemination. Passive transfer of immune convalescent serum, but not recombinant IFN{gamma}, reduced bacterial burden in both systemic and mucosal tissues in IFN{gamma}-/- x {micro}MT mice. Moreover, we observed a reduction of bacterial shedding of more than two orders of magnitude in IFN{gamma}-/- x {micro}MT mice following both Chlamydia muridarum and Chlamydia trachomatis infections. Lastly, protective immunity against C. muridarum reinfection was completely abrogated in the absence of IFN{gamma} and B cells. Our results suggest that IFN{gamma} and B cells synergize to combat bacterial dissemination, while an IFN{gamma} and B cell-independent mechanism exists for host resistance to Chlamydia in the FRT.

immunology↗

bioRxiv2020

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.

immunology↗