Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties.
Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties.
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
C Preston
CP
Neff
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Matthew E
ME
Rhodes
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kathleen L
KL
Arnolds
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Colm B
CB
Collins
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jody
J
Donnelly
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nichole
N
Nusbacher
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Paul
P
Jedlicka
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jennifer M
JM
Schneider
Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Martin D
MD
McCarter
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Michael
M
Shaffer
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Sarkis K
SK
Mazmanian
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: brent.palmer@ucdenver.edu.
Brent E
BE
Palmer
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: catherine.lozupone@ucdenver.edu.
Catherine A
CA
Lozupone
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001419:Bacteria / Q000737:chemistry*; D003092:Colitis / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D011135:Polysaccharides, Bacterial; D016753:Interleukin-10
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