A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency.

Autor: Lu Q; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Hitch TCA; Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany., Zhou JY; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Dwidar M; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44195, USA., Sangwan N; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44195, USA., Lawrence D; Department of Medicine, Washington University, Saint Louis, MO 63110, USA., Nolan LS; Department of Medicine, Washington University, Saint Louis, MO 63110, USA., Espenschied ST; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Newhall KP; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Han Y; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Karell PE; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Salazar V; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Baldridge MT; Department of Medicine, Washington University, Saint Louis, MO 63110, USA., Clavel T; Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany., Stappenbeck TS; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Sep 27; Vol. 385 (6716), pp. eadk2536. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1126/science.adk2536
Abstrakt: Harnessing the microbiome to benefit human health requires an initial step in determining the identity and function of causative microorganisms that affect specific host physiological functions. We show a functional screen of the bacterial microbiota from mice with low intestinal immunoglobulin A (IgA) levels; we identified a Gram-negative bacterium, proposed as Tomasiella immunophila , that induces and degrades IgA in the mouse intestine. Mice harboring T. immunophila are susceptible to infections and show poor mucosal repair. T. immunophila is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid. It delivers immunoglobulin-degrading proteases into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. This work indicates a role for symbionts in immunodeficiency, which might be applicable to human disease.
Databáze: MEDLINE
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