Gonococcal modulation of host immune responses during single and dual infections

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Neisseria gonorrhoeae and Chlamydia trachomatis are two of the most common sexually transmitted pathogens in the world. N. gonorrhoeae depends on numerous, highly adapted host-pathogen interactions to persist in the human urogenital tract. Uncomplicated gonococcal infection of the urethra or cervix leads to limited, and non- protective, adaptive immune responses. The mechanisms by which N. gonorrhoeae evades host immunity are thought to include both antigenic variation and active manipulation of immune system signaling by the infecting bacteria. Our preliminary data demonstrates that N. gonorrhoeae inhibits the ability of antigen presenting cells to stimulate CD4+ T lymphocyte proliferation. N. gonorrhoeae accomplishes this through the shedding of outer membrane vesicles and anhydrous peptidoglycan fragments from its cell wall. Some C. trachomatis infected individuals appear to develop protective immunity to the infection. In animal models, CD4+ T lymphocytes directed towards chlamydial antigens can mediate protective immuniity in chlamydial infection. Our preliminary data suggest that N. gonorrhoeae is able to cross suppress T lymphocyte proliferation directed towards chlamydial antigens. In this proposal we propose to identify the signaling mechanisms and consequences to the immune response that are activated by N. gonorrheoeae. Further we will determine the impact of N. gonorrhoeae-mediated immune suppression in both N. gonorrhoeae infection and N. gonorrhoeae/Chlamydia co-infection.