Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro

Neisseria gonorrhoeae is an obligate human pathogen that represents a significant health concern, particularly in the developing world. Although generally associated with an acute inflammatory infection of urogenital epithelia cells, infections have been noted in multiple tissues and many infected individuals can become asymptomatic carriers. Few studies of immune response to N. gonorrhoeae infection in peripheral blood have evaluated the production of T helper cytokines (TH1/TH2) induced early after infection. We developed a quantitative realtime PCR assay based on the gonococcal rmpIII gene to monitor dose-response effects of infection on cytokine release from peripheral blood mononuclear cells (PBMCs). We observed upregulation of CD69 transcription and surface CD25 expression on lymphocytes, consistent with early T-cell activation. We observed dosage-dependent transcription of the chemotactic factor IL-8 and previously unreported activation of the chemoattractant MCP-2. Multiplex analysis of broad cytokine protein production revealed a differential increase in the TH1 and TH2 associated cytokines: IL-2, IL-4, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha and MCP-1. Markov models of protein accumulation implicated a cross-regulated response to infection, notably for IL-8, IL-10 and IL-12. Taken together, the cytokine profile we observed early in response to whole gonococcal bacteria was broader than has been previously described and may have relevance for the contribution of antagonistic signaling events early in infection and in understanding peripheral immune mechanisms engaged to control infection.