Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 36th and Hamilton Walk, 230 John Morgan Building, Philadelphia, PA 19104-6082, USA.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Cell Host Microbe. 2018 Mar 14;23(3):302-311.e3. doi: 10.1016/j.chom.2018.01.005. Epub 2018 Feb 22.
Serum immunoglobulin A (IgA) antibodies are readily detected in mice and people, but the mechanisms underlying the induction of serum IgA and its role in host protection remain uncertain. We report that select commensal bacteria induce several facets of systemic IgA-mediated immunity. Exposing conventional mice to a unique but natural microflora that included several members of the Proteobacteria phylum led to T cell-dependent increases in serum IgA levels and the induction of large numbers of IgA-secreting plasma cells in the bone marrow. The resulting serum IgA bound to a restricted collection of bacterial taxa, and antigen-specific serum IgA antibodies were readily induced after intestinal colonization with the commensal bacterium Helicobacter muridarum. Finally, movement to a Proteobacteria-rich microbiota led to serum IgA-mediated resistance to polymicrobial sepsis. We conclude that commensal microbes overtly influence the serum IgA repertoire, resulting in constitutive protection against bacterial sepsis.
血清免疫球蛋白 A（IgA）抗体在小鼠和人类中很容易被检测到，但诱导血清 IgA 的机制及其在宿主保护中的作用仍不确定。我们报告说，某些共生细菌可诱导多种系统性 IgA 介导的免疫反应。将常规小鼠暴露于一种独特但天然的微生物群，其中包括几个变形菌门的成员，导致 T 细胞依赖性血清 IgA 水平升高，并在骨髓中诱导大量 IgA 分泌浆细胞。由此产生的血清 IgA 与有限的细菌分类群结合，并且在用共生细菌鼠螺杆菌定植肠道后，可轻易诱导抗原特异性血清 IgA 抗体。最后，移居到富含变形菌的微生物群中会导致血清 IgA 介导的对抗多种微生物败血症的抵抗力。我们的结论是，共生微生物明显影响血清 IgA 库，从而对细菌性败血症产生固有保护作用。
