Gamma Interferon Is Required for<i>Chlamydia</i>Clearance but Is Dispensable for T Cell Homing to the Genital Tract

Abstract

While there is no effective vaccine against <i>Chlamydia trachomatis</i> infection, previous work has demonstrated the importance of <i>C. trachomatis</i>-specific CD4⁺ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host's ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against <i>C. trachomatis</i> Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ^-/-, and IFN-γR^-/- NR1 T cells specifically home to sections in the genital tract that contain <i>C. trachomatis</i> We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing <i>C. trachomatis</i> infection.<b>IMPORTANCE</b><i>Chlamydia trachomatis</i> is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4⁺ T cells are critical for <i>Chlamydia</i> clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to <i>C. trachomatis</i> Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against <i>C. trachomatis</i>.