ena-STUDY-Institute for Biomedical Sciences - Georgia State University-19-09-2019-05:23:06:134-62
Segmented filamentous bacteria prevent and cure rotavirus infection
Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. While RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immune-deficient mice, which we hypothesized reflected select microbes protecting against RV. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. RV-protecting microbiotas were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) was sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously-defined RV-impeding factors including interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.
Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. While RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immune-deficient mice, which we hypothesized reflected select microbes protecting against RV. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. RV-protecting microbiotas were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) was sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously-defined RV-impeding factors including interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.