Peptidoglycan fragment release and NOD activation by commensalNeisseriaspecies from humans and other animals

Abstract

AbstractNeisseria gonorrhoeae, a human restricted pathogen, releases inflammatory peptidoglycan (PG) fragments that contribute to the pathophysiology of pelvic inflammatory disease. The genusNeisseriais also home to multiple species of human- or animal-associatedNeisseriathat form part of the normal microbiota. Here we characterized PG release from the human-associated nonpathogenic speciesN. lactamicaandN. mucosaand animal-associatedNeisseriafrom macaques and wild mice. AnN. mucosastrain and anN. lactamicastrain were found to release limited amounts of the pro-inflammatory monomeric PG fragments. However, a single amino acid difference in the PG fragment permease AmpG resulted in increased PG fragment release in a secondN. lactamicastrain examined.Neisseriaisolated from macaques also showed significant release of PG monomers. The mouse colonizerN. musculiexhibited PG fragment release similar to that seen inN. gonorrhoeaewith PG monomers being the predominant fragments released. All the human-associated species were able to stimulate NOD1 and NOD2 responses.N. musculiwas a poor inducer of mouse NOD1, butldcAmutation increased this response. The ability to genetically manipulateN. musculiand examine effects of different PG fragments or differing amounts of PG fragments during mouse colonization will lead to a better understanding of the roles of PG inNeisseriainfections. Overall, we found that only some nonpathogenicNeisseriahave diminished release of pro-inflammatory PG fragments, and there are differences even within a species as to types and amounts of PG fragments released.