Sometimes-pathogenic Neisseria are constantly invoking immune response in humans

 Fluorescent antibody stain of  Neisseria gonorrhoeae .

Fluorescent antibody stain of Neisseria gonorrhoeae.

Bacteria from the genus Neisseria exist as normal commensals in greater than 95% of adults.  That being said, two strains, Neisseria meningitides (a cause of bacterial meningitis) and Neisseria gonorrhoeae (the cause of gonorrhea),are known pathogens, although these too can often asymptomatic.  A new study published last week in Science suggests that although asymptomatic, Neisseria may always be inducing an autoimmune response, via a metabolite they are constantly producing and releasing into the environment. 

Using genetic approaches, scientists from the University of Toronto identified the inflammation-inducing metabolite as heptose-1,7-bisphosphate (HBP), which prior to the study had not been implicated as causing an immune response.  To prove its effect, the researchers injected the metabolite into mice and showed that these mice displayed inflammation almost immediately.  The scientists recognized that this metabolite is actually produced by many bacteria, and wondered if these others were causing harm as well.  Using mouse studies though, they demonstrated that other bacteria do not release it from their cells into the environment, so these bacteria only induce a response when they are lysed.  Thus far only Neisseria have been shown to produce and release this metabolite, which is important because it means as long as they are growing they are constantly producing an immune response. 

The scientists also discovered the immune pathway by which HMP triggers a response: the TRAF-interacting protein with forkhead-associated domain (TIFA).  Interestingly, it has been known for many years that infection with N. meningitidis or N. gonorrhoeae increases HIV shedding and transmission, but the reason was still a mystery.  The scientists figured out this connection when they recognized that HIV actually use the TIFA pathway to reproduce.  They observed that these bacteria invoke the TIFA response via HBP, which gives the HIV the proper cells it needs to replicate.

Given what we know about the effects of chronic inflammation and its effects on many diseases these findings could be very important.  Perhaps there is no such thing as a nonpathogenic Neisseria, and its existence in ‘healthy’ guts may not be so healthy after all.

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