Disruption of Genes Encoding Putative Zwitterionic Capsular Polysaccharides of Diverse Intestinal Bacteroides Reduces the Induction of Host Anti-Inflammatory Factors

• Kathleen L. Arnolds ^[1] ; Eiko Yamada ^[2] ; C. Preston Neff ^[2] ; Jennifer M. Schneider ^[2] ; Brent E. Palmer ^[2] ; Catherine A. Lozupone ^[2]
  1. [1] Department of Immunology and Microbiology, University of Colorado Anschutz, Aurora, CO, USA
  2. [2] Department of Medicine, University of Colorado Anschutz, Aurora, CO, USA
• Localización: Microbial ecology, ISSN-e 1432-184X, ISSN 0095-3628, Vol. 85, Nº. 4, 2023, págs. 1620-1629
• Idioma: inglés
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• Resumen

  • Bacterial zwitterionic capsular polysaccharides (ZPS), such as polysaccharide A (PSA) of the intestinal commensal Bacteroides fragilis, have been shown to modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). We previously used a genomic screen to identify diverse host-associated bacteria with the predicted genetic capacity to produce ZPSs related to PSA of B. fragilis and hypothesized that genetic disruption (KO) of a key functional gene within these operons would reduce the anti-inflammatory activity of these bacteria. We found that ZPS-KO bacteria in two common gut commensals, Bacteroides uniformis and Bacteroides cellulosilyticus, had a reduced ability to induce Tregs and IL-10 in stimulations of human peripheral blood mononuclear cells (PBMCs). Additionally, we found that macrophage stimulated with either wildtype B. fragilis or B. uniformis produced significantly more IL-10 than KOs, indicating a potentially novel function of ZPS of shifting the cytokine response in macrophages to a more anti-inflammatory state. These findings support the hypothesis that these related ZPS may represent a shared strategy to modulate host immune responses.