Segmented filamentous bacteria prevent and cure rotavirus infection. Segmented filamentous bacteria prevent and cure rotavirus infection

Enteric viruses encounter epithelial cells amidst diverse microbiota. We hypothesized that our unintentional generation of rotavirus (RV)-resistant Rag1-KO mice reflected microbiota composition influencing RV infection. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. Interrogation of RV-protecting microbiotas via heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germfree mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of lymphocytes (innate and adaptive), interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover, which likely contributed to reducing RV burden. Yet, incubation of RV with SFB-containing feces reduced its infectivity in vitro, suggesting possible direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.

肠道病毒于复杂多样的微生物群微环境中与上皮细胞相互作用。我们推测，本研究中意外获得的轮状病毒（rotavirus, RV）抗性重组激活基因1敲除（Rag1-KO）小鼠，其表型反映了微生物群组成对RV感染的调控作用。据此，该RV抗性可通过同笼饲养与粪便移植实现传递。通过热处理、过滤及抗菌试剂对RV保护性微生物群展开解析，随后将其有限稀释后移植至无菌小鼠（germfree mice）体内，并对粪便样本进行DNA测序，结果显示分段丝状细菌（segmented filamentous bacteria, SFB）发挥核心调控作用：该菌足以使小鼠抵御RV感染及其伴随的腹泻症状。此种保护作用不依赖于淋巴细胞（天然免疫与适应性免疫）、干扰素、IL-17及IL-22。SFB在回肠定植可诱导宿主基因表达发生改变，并加速上皮细胞更新，这可能有助于降低RV载量。然而，将RV与含SFB的粪便共同孵育可在体外降低其感染性，提示存在对RV的直接中和作用。综上，SFB可不依赖免疫细胞，为宿主抵御特定肠道病毒感染及其伴随的腹泻疾病提供保护。