FIGURE 2.

Impact of Neisseria gonorrhoeae infection on establishment of HIV infection in a seronegative individual. The gonococcus may cause an increased susceptibility to HIV infection through a combination of the inflammation-induced damage of the epithelial barrier and increased inflammation within the genital microenvironment. This allows enhanced entry of HIV into the submucosa, either through dendritic cells (DCs) that are sampling the mucosal environment or through disrupted epithelium. Given that the gonococci cause an intense localized inflammation, as evidenced by an extensive neutrophil influx to the site of infection, CD4 T-cells that are recruited to the site of infection will be activated by the cytokines and other inflammatory mediators so as to become optimal targets for HIV infection and replication. Macrophage that are recruited to the site of gonococcal infection may also produce pro-inflammatory cytokines and chemokines to simultaneously activate local CD4 T-cells and recruit further HIV-receptive target cells. Furthermore, the macrophages or DCs can take up the HIV present in the genital microenvironment and travel to distal secondary lymphoid organs where they can further promote HIV infection of CD4 T-cells in these regions.