The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines. Transferring a restricted community of cultivable intestinal commensals from protected into susceptible mice decreases S. Typhimurium tissue colonization and consequently disease severity. This reduced tissue colonization, along with ameliorated weight loss and prolonged survival, depends on microbiota-enhanced IFNγ production, as IFNγ-deficient mice do not exhibit protective effects. Innate cells and CD4⁺ T cells increase in number and show high levels of IFNγ after transfer of the commensal community. Thus, distinct microbiota members prevent intestinal Salmonella infection by enhancing antibacterial IFNγ responses.

微生物群通过竞争代谢物，产生抑制性物质和引发保护性免疫应答，从而有助于抵抗入侵的病原体。但是，促进宿主抗性和免疫介导的保护作用的特定共生细菌仍然很难捉摸。使用具有不同微生物群特征的等基因小鼠品系，我们证明了由肠伤寒沙门氏菌感染诱导的疾病严重程度受到各个品系中微生物群组成的强烈调节。将受保护的肠道共生菌的受限群落从受保护的小鼠转移到易感小鼠中会降低S。鼠伤寒组织定植，因此疾病严重。这种组织定植的减少，以及减轻的体重减轻和延长的生存期，取决于微生物群增强的IFNγ产生，因为缺乏IFNγ的小鼠没有表现出保护作用。先天性细胞和CD4 ⁺ T细胞的数量增加，并在共生群落转移后显示出高水平的IFNγ。因此，不同的微生物群成员通过增强抗菌素IFNγ反应来预防肠道沙门氏菌感染。