Figure 4: Neisseria gonorrhoeae evades and modulates the innate and adaptive immune system.

a) During infection, both the alternative and classical complement pathways may be activated by N. gonorrhoeae. N. gonorrhoeae binds complement proteins to prevent opsonization and killing by membrane attack complexes¹⁸, as well as siaylates its LOS to hide from the complement system¹⁷⁷. N. gonorrhoeae binds host Factor H and C4bp, becoming serum resistant by presenting as ‘self’ and shielding itself from complement recognition^97,178 N. gonorrhoeae also binds to the alternative complement pathway receptor CR3 and the receptor for iC3b, a process thought to aid in epithelial cell invasion¹⁰⁰. N. gonorrhoeae binds C3b through Lipid A on its LOS, rapidly inactivating C3b to iC3b through factor I¹⁷⁹. b) N. gonorrhoeae is able to survive in and around macrophages and neutrophils during infection, and modulate the immune activating properties of dendritic cells^{114,116,122,124,136,164,180}. In macrophages, N. gonorrhoeae is able to survive inside the phagosome and modulate apoptosis and production of inflammatory cytokines ¹¹⁴. The bacteria polarize macrophages, resulting in macrophages less capable of T cell activation¹¹⁶, and similarly, dendritic cells exposed to N. gonorrhoeae are less capable of stimulating T cell proliferation¹³⁶. The interactions of N. gonorrhoeae and neutrophils is complex and is discussed in detail in the text. c) N. gonorrhoeae infection does not generate immunological memory, due to the ability of N. gonorrhoeae to antigenically and phase vary its surface structures including Type IV pili, Opa proteins, and LOS. In addition, N. gonorrhoeae modulates the adaptive immune response by suppressing T helper cell proliferation and subsequent activation through influencing cytokine production^134,135,181.