Modulation of HIV transmission by Neisseria gonorrhoeae: molecular and immunological aspects

Abstract

Neisseria gonorrhoeae (GC), a major cause of pelvic inflammatory disease, can facilitate HIV transmission. In response to GC infection, genital epithelial cells can produce cytokines, chemokines and defensins to modulate HIV infection and infectivity. GC can also induce the production of cytokines and chemokines in monocytes and modulate T cell activation. In vivo, an increase in the number of endocervical CD4+ T cells has been found in GC-infected women. Additionally, GC appears to modulate HIV-specific immune responses in HIV-exposed sex workers. Interestingly, in vitro, GC exhibits HIV enhancing or inhibitory effects depending on the HIV target cells. This review summarizes molecular and immunological aspects of the modulation of HIV infection and transmission by GC. Future studies using a multi-cellular system or in animal models will offer insight into the mechanisms by which GC increases HIV transmission.

Fig. (1). GC induces cytokine production through TLR2 and TLR4 signaling pathways

Formation of the TLR4-MD2-LOS complex can activate MyD88-dependent or TRIP-dependent pathways. The GC bacterial components, Porin and lipoprotein, induce NF-kB activation and cytokine production through MyD88-depedent pathways.