Qiuhe Lu, Thomas C. A. Hitch, Julie Y. Zhou, Mohammed Dwidar, Naseer Sangwan, Dylan Lawrence, Lila S. Nolan, Scott T. Espenschied, Kevin P. Newhall, Yi Han, Paul E. Karell, Vanessa Salazar, Megan T. Baldridge, Thomas Clavel, Thaddeus S. Stappenbeck
{"title":"A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency","authors":"Qiuhe Lu, Thomas C. A. Hitch, Julie Y. Zhou, Mohammed Dwidar, Naseer Sangwan, Dylan Lawrence, Lila S. Nolan, Scott T. Espenschied, Kevin P. Newhall, Yi Han, Paul E. Karell, Vanessa Salazar, Megan T. Baldridge, Thomas Clavel, Thaddeus S. Stappenbeck","doi":"10.1126/science.adk2536","DOIUrl":null,"url":null,"abstract":"<div >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 <i>Tomasiella immunophila</i>, that induces and degrades IgA in the mouse intestine. Mice harboring <i>T. immunophila</i> are susceptible to infections and show poor mucosal repair. <i>T. immunophila</i> 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.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":null,"pages":null},"PeriodicalIF":44.7000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.adk2536","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
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