Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

Zhenda Shi; Jun Zou; Zhan Zhang; Xu Zhao; Juan Noriega; Benyue Zhang; Chunyu Zhao; Harshad Ingle; Kyle Bittinger; Lisa M. Mattei; Andrea J. Pruijssers; Richard K. Plemper; Timothy J. Nice; Megan T. Baldridge; Terence S. Dermody; Benoit Chassaing; Andrew T. Gewirtz

doi:10.1016/j.cell.2019.09.028

Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

Zhenda Shi
, Jun Zou
, Zhan Zhang
, Xu Zhao
, Juan Noriega
, Benyue Zhang
, Chunyu Zhao
, Harshad Ingle
, Kyle Bittinger
, Lisa M. Mattei
, Andrea J. Pruijssers
, Richard K. Plemper
, Timothy J. Nice
, Megan T. Baldridge
, Terence S. Dermody
, Benoit Chassaing
, Andrew T. Gewirtz

Molecular Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

150 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	644-658.e13
Journal	Cell
Volume	179
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2019.09.028
State	Published - Oct 17 2019

Funding

This work was supported by NIH grants DK099071 (to A.T.G.), DK083890 (to A.T.G.), and AI038296 (to T.S.D.). B.C. is supported by Crohn’s and Colitis Foundation and the Kenneth Rainin Foundation . J.Z. is supported by the American Diabetes Association . H.I. is supported by the Children’s Discovery Institute of Washington University and a St. Louis Children’s Hospital postdoctoral research grant ( MI-F-2018-712 ). M.T.B. was supported by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital ( MI-II-2019-790 ). We thank Solomiia Khomandiak for technical support and Yang Wu for helpful advice and figure preparation. This work was supported by NIH grants DK099071 (to A.T.G.), DK083890 (to A.T.G.), and AI038296 (to T.S.D.). B.C. is supported by Crohn's and Colitis Foundation and the Kenneth Rainin Foundation. J.Z. is supported by the American Diabetes Association. H.I. is supported by the Children's Discovery Institute of Washington University and a St. Louis Children's Hospital postdoctoral research grant (MI-F-2018-712). M.T.B. was supported by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital (MI-II-2019-790). We thank Solomiia Khomandiak for technical support and Yang Wu for helpful advice and figure preparation. Z.S. conceived, designed, and executed the study. J.Z. Z.Z. J.N. and B.Z. provided advice and technical assistance. X.Z. T.J.N. A.J.P. and T.S.D. provided reagents and advice. C.Z. L.M.M. and K.B. performed SFB genomics. H.I. and M.T.B. performed experiments regarding type 3 IFN. R.K.P. performed experiments on IAV and VSV. B.C. performed microbiota analyses and gnotobiotics. A.T.G. provided overall guidance and, together with Z.S. and T.S.D. prepared the manuscript. The authors declare no competing interests.

Funders	Funder number
Children's Discovery Institute of Washington University	SFB genomics
Children’s Discovery Institute of Washington University
Crohn’s and Colitis Foundation Genetics Initiative
Children’s Discovery Institute, St. Louis Children’s Hospital	MI-F-2018-712, MI-II-2019-790
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	DK083890, AI038296, DK099071
American Diabetes Association
Kenneth Rainin Foundation
Crohn's and Colitis Foundation
Alzheimer Society of B.C.
Institute for Functional Nanomaterials

Keywords

fecal transplant
germ-free mice
infectious diarrhea
microbiota-virus interactions
rotavirus
segmented filamentous bacteria
viral gastroenteritis

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2019.09.028

Cite this

Shi, Z., Zou, J., Zhang, Z., Zhao, X., Noriega, J., Zhang, B., Zhao, C., Ingle, H., Bittinger, K., Mattei, L. M., Pruijssers, A. J., Plemper, R. K., Nice, T. J., Baldridge, M. T., Dermody, T. S., Chassaing, B., & Gewirtz, A. T. (2019). Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection. Cell, 179(3), 644-658.e13. https://doi.org/10.1016/j.cell.2019.09.028

@article{fa4b4613f3aa479fae15aeb9dd0647b7,

title = "Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection",

abstract = "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.",

keywords = "fecal transplant, germ-free mice, infectious diarrhea, microbiota-virus interactions, rotavirus, segmented filamentous bacteria, viral gastroenteritis",

author = "Zhenda Shi and Jun Zou and Zhan Zhang and Xu Zhao and Juan Noriega and Benyue Zhang and Chunyu Zhao and Harshad Ingle and Kyle Bittinger and Mattei, \{Lisa M.\} and Pruijssers, \{Andrea J.\} and Plemper, \{Richard K.\} and Nice, \{Timothy J.\} and Baldridge, \{Megan T.\} and Dermody, \{Terence S.\} and Benoit Chassaing and Gewirtz, \{Andrew T.\}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = oct,

day = "17",

doi = "10.1016/j.cell.2019.09.028",

language = "English (US)",

volume = "179",

pages = "644--658.e13",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "3",

}

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.

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 - https://www.scopus.com/pages/publications/85073165057

UR - https://www.scopus.com/pages/publications/85073165057#tab=citedBy

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 -

Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this