A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency

• 成果类型: Article
• 署名作者: Lu, Qiuhe; Hitch, Thomas C. A.; Zhou, Julie Y.; Dwidar, Mohammed; Sangwan, Naseer; Lawrence, Dylan; Nolan, Lila S.; Espenschied, Scott T.; Newhall, Kevin P.; Han, Yi; Karell, Paul E.; Salazar, Vanessa; Baldridge, Megan T.; Clavel, Thomas; Stappenbeck, Thaddeus S.
• 署名单位: Cleveland Clinic Foundation; RWTH Aachen University; RWTH Aachen University Hospital; Cleveland Clinic Foundation; Cleveland Clinic Foundation; Washington University (WUSTL)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9571
• DOI: 10.1126/science.adk2536
• 发表日期: 2024-09-27
• 关键词: fecal iga levels; immune-responses; bacteria; microbiota; colonization; biogenesis; proteinase; mice

摘要

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.