4.8 Article

Capsular polysaccharide correlates with immune response to the human gut microbe Ruminococcus gnavus

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.2007595118

关键词

Ruminococcus gnavus; capsular polysaccharide; capsule; inflammation; dendritic cell

资金

  1. NIH [R01-AT009708, F32-GM126650]
  2. Chemical Sciences, Geosciences, and Biosciences Divisions of the Office of Basic Energy Sciences, US Department of Energy Grant [DE-SC0015662]

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Research has shown that some isolates of R. gnavus produce a capsular polysaccharide that promotes tolerogenic immune responses, while isolates lacking a capsule trigger robust proinflammatory responses. In mouse experiments, it was also found that mice colonized with an isolate of R. gnavus lacking a capsule showed increased gut inflammation.
Active inflammatory bowel disease (IBD) often coincides with increases of Ruminococcus gnavus, a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of R. gnavus to identify molecular mechanisms that would link R. gnavus to inflammation. Here, we show that only some isolates of R. gnavus produce a capsular polysaccharide that promotes a tolerogenic immune response, whereas isolates lacking functional capsule biosynthetic genes elicit robust proinflammatory responses in vitro. Germ-free mice colonized with an isolate of R. gnavus lacking a capsule show increased measures of gut inflammation compared to those colonized with an encapsulated isolate in vivo. These observations in the context of our earlier identification of an inflammatory cell-wall polysaccharide reveal how some strains of R. gnavus could drive the inflammatory responses that characterize IBD.

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