Received May 12, 2017; Accepted August 19, 2017; Published September 28, 2017
http://dx.doi.org/10.18081/2333-5106/015-04/295-312
Yan Tsuchimoto; Rong Hwang; Song Chen; Xiang Liu
Abstract
Neisseria gonorrhoeae (GC) causes the second most frequently reported sexually transmitted disease worldwide. Global antibiotic resistance limits treatment options, so understanding immunity to GC is key. We have recently discovered an unappreciated role for IFN-γ during genital GC infection. We have uncovered an essential role for IFN-γ in broadening and promoting the endocervical epithelial cell intrinsic IFN-signaling response and downstream signaling in the absence of IFN-γR signaling. Paradoxically, responses in IFN-γR KO mice are delayed, implying an alternative early IFN-γ signal on IP-10 or signaling-independent function. The purpose of this study was to define the mechanism and importance of IFN-γ during GC infection. Given that B cells need interactions with both antigen and costimulatory molecules, it is not well understood how mucosal antigen presenting cells might activate these cells. We would like to define the contribution of host IFN-γ to these events. Our long-term goal is to dissect the innate and adaptive host immune responses during genital gonococcal infection to identify correlates of protection and inform rational vaccine design. The goal of the current study was to determine how early IFN-γ signals are important for early innate antineisseriae defenses. To accomplish our objectives, we have 1) treated normal animals with exogenous IFN-γ and looked for direct IFN-γR signaling in early epithelium, 2) identified alternative sources of the early IFN-γ signal, 3) defined whether these early signals support IFN-γ-dependent antigonococcal activities and 4) clarified imd signaling during infection with nongonococcal populations.
Keywords: Gonorrhea; IFN-γ; Innate B cells; Pathogen
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