The Cytokine Response to Pathogen N. gonorrhoeae and Commensal N. elongata

Abstract

The Neisseria genus is predominantly comprised of commensals that are asymptomatically carried by humans. The pathogens N. gonorrhoeae (Ngo) and N. meningitidis are often asymptomatically carried, yet are causative agents of gonorrhoeae and meningitis respectively. N. elongata (Nel) is a commensal of the nasopharynx, and the most evolutionarily distal commensal to Ngo. It is unknown what factors drive commensal versus pathogenic lifestyle. All Neisseria contain genes for the Type IV Pilus, a retractile appendage important for modulating Ngo-host interactions. Ngo pilus retraction stimulates a cytoprotective environment that promotes Ngo carriage and host cell survival. Nel also express functional pili, but it is unknown if or how retraction is implicated in Nel-host interactions. Here we investigate how commensal Nel and pathogen N. gonorrhoeae differentially modulate the host via pilus retraction. We show that Nel pilus retraction is implicated in adherence and invasion of host cells, similar to Ngo. Nel pilus retraction stimulates a cytokine environment that is distinct from Ngo in vitro. This cytokine environment is maintained via EGFR and DUSP-1 signaling. We conclude that Nel pilus retraction is important for tuning the host-cell response to Nel carriage, and may promote a pro-commensal cytokine environment.