TY - JOUR
T1 - Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection
AU - Shi, Zhenda
AU - Zou, Jun
AU - Zhang, Zhan
AU - Zhao, Xu
AU - Noriega, Juan
AU - Zhang, Benyue
AU - Zhao, Chunyu
AU - Ingle, Harshad
AU - Bittinger, Kyle
AU - Mattei, Lisa M.
AU - Pruijssers, Andrea J.
AU - Plemper, Richard K.
AU - Nice, Timothy J.
AU - Baldridge, Megan T.
AU - Dermody, Terence S.
AU - Chassaing, Benoit
AU - Gewirtz, Andrew T.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10/17
Y1 - 2019/10/17
N2 - Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota 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) were 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 the 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 confer protection against certain enteric viral infections and associated diarrheal disease.
AB - Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota 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) were 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 the 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 confer protection against certain enteric viral infections and associated diarrheal disease.
KW - fecal transplant
KW - germ-free mice
KW - infectious diarrhea
KW - microbiota-virus interactions
KW - rotavirus
KW - segmented filamentous bacteria
KW - viral gastroenteritis
UR - http://www.scopus.com/inward/record.url?scp=85073165057&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2019.09.028
DO - 10.1016/j.cell.2019.09.028
M3 - Article
C2 - 31607511
AN - SCOPUS:85073165057
SN - 0092-8674
VL - 179
SP - 644-658.e13
JO - Cell
JF - Cell
IS - 3
ER -