Effective clearance of Chlamydia from the female reproductive tract in the absence of T-bet+ Th1 cells

Abstract

Abstract Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are thought to be vital for bacterial clearance, due to their capacity to secrete IFN-γ, but Th1 responses as defined by the master transcription factor T-bet had not yet been fully interrogated in primary infection. Here, we investigated T-bet and IFN-γ involvement in primary infection clearance. We found that IFN-γ producing CD4+ T cells from the FRT exhibited surprisingly low levels of T-bet throughout primary infection, indicating low involvement of classical T-bet+ Th1 cells. Mice deficient for T-bet either globally or specifically in CD4+ cells both competently cleared infection along wild-type kinetics. T-bet-deficient mice also showed significant skewing towards Th17 responses, indicating potential compensation pathways through alternate Th fates. On the other hand, IFN-γ-, and IFN-γR-deficient mice resolved much of FRT infection, but experienced systemic dissemination and 100% mortality with an average median survival of approximately 4 weeks. Together, this indicates that while IFN-γ is important to protect mice from death, classical T-bet+ Th1 cells are ultimately not required for primary clearance. Studies are underway to examine which alternative CD4 T cell mechanisms contribute to bacterial clearance within the FRT. Supported by grants from NIH (RO1 A1103422, T32 AI060555)