| Neisseria gonorrhoeae is a human-restricted pathogen associated with increasing morbidity as antibiotic-resistant strains spread globally. N. gonorrhoeae possesses sophisticated mechanisms to survive the host immune response, in which CEACAM1, a host receptor, plays a central role. Gonococcal Opa protein-bound CEACAM1 inhibits host cells such as CD4+ T cells. This inhibitory activity has been attributed to recruitment of protein tyrosine phosphatases but evidence suggests CEACAM1 modulates other signaling pathways. In Chapter 2, I found that the inositol phosphatases, SHIP-1 and SHIP-2, associated with gonococcal-bound CEACAM1, as did the inositol signaling lipids, PIP3 and 3,4-PIP2. To explore the functional outcome of the SHIP-CEACAM1 association, I investigated the response of human macrophages to gonococci in Chapter 3. I found that N. gonorrhoeae skews macrophages to the M1 phenotype and I discovered Opa-specific differences in macrophage cytokine secretion. This work expands the knowledge of gonococcal immune evasion and CEACAM1's inhibitory role in that strategy. |
