Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany.
Science. 2024 Sep 27;385(6716):eadk2536. doi: 10.1126/science.adk2536.
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 , that induces and degrades IgA in the mouse intestine. Mice harboring are susceptible to infections and show poor mucosal repair. 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.
利用微生物组有益于人类健康，首先需要确定影响特定宿主生理功能的致病微生物的身份和功能。我们对肠道免疫球蛋白 A（IgA）水平较低的小鼠的细菌微生物组进行了功能筛选；我们鉴定出一种革兰氏阴性菌，即 ，它在小鼠肠道中诱导和降解 IgA。携带 的小鼠易受感染，且粘膜修复能力差。 是细菌细胞壁氨基糖 N-乙酰胞壁酸的营养缺陷型。它将免疫球蛋白降解蛋白酶递送到外膜囊泡中，这些囊泡优先降解具有κ但不具有λ轻链的啮齿动物抗体。这项工作表明共生体在免疫缺陷中的作用，这可能适用于人类疾病。
