Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18

Benyue Zhang; Benoit Chassaing; Zhenda Shi; Robin Uchiyama; Zhan Zhang; Timothy L. Denning; Sue E. Crawford; Andrea J. Pruijssers; Jason A. Iskarpatyoti; Mary K. Estes; Terence S. Dermody; Wenjun Ouyang; Ifor R. Williams; Matam Vijay-Kumar; Andrew T. Gewirtz

doi:10.1126/science.1256999

Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18

Benyue Zhang, Benoit Chassaing, Zhenda Shi, Robin Uchiyama, Zhan Zhang, Timothy L. Denning, Sue E. Crawford, Andrea J. Pruijssers, Jason A. Iskarpatyoti, Mary K. Estes, Terence S. Dermody, Wenjun Ouyang, Ifor R. Williams, Matam Vijay-Kumar, Andrew T. Gewirtz

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

196 Scopus citations

Abstract

Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent. Copyright2014 by the American Association for the Advancement of Science; all rights reserved.

Original language	English (US)
Pages (from-to)	861-865
Number of pages	5
Journal	Science
Volume	346
Issue number	6211
DOIs	https://doi.org/10.1126/science.1256999
State	Published - Nov 14 2014

All Science Journal Classification (ASJC) codes

General

Access to Document

10.1126/science.1256999

Cite this

Zhang, B., Chassaing, B., Shi, Z., Uchiyama, R., Zhang, Z., Denning, T. L., Crawford, S. E., Pruijssers, A. J., Iskarpatyoti, J. A., Estes, M. K., Dermody, T. S., Ouyang, W., Williams, I. R., Vijay-Kumar, M., & Gewirtz, A. T. (2014). Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science, 346(6211), 861-865. https://doi.org/10.1126/science.1256999

@article{d75732b90b1945ba8ebac1b2a926ab86,

title = "Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18",

abstract = "Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent. Copyright2014 by the American Association for the Advancement of Science; all rights reserved.",

author = "Benyue Zhang and Benoit Chassaing and Zhenda Shi and Robin Uchiyama and Zhan Zhang and Denning, {Timothy L.} and Crawford, {Sue E.} and Pruijssers, {Andrea J.} and Iskarpatyoti, {Jason A.} and Estes, {Mary K.} and Dermody, {Terence S.} and Wenjun Ouyang and Williams, {Ifor R.} and Matam Vijay-Kumar and Gewirtz, {Andrew T.}",

year = "2014",

month = nov,

day = "14",

doi = "10.1126/science.1256999",

language = "English (US)",

volume = "346",

pages = "861--865",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6211",

}

Zhang, B, Chassaing, B, Shi, Z, Uchiyama, R, Zhang, Z, Denning, TL, Crawford, SE, Pruijssers, AJ, Iskarpatyoti, JA, Estes, MK, Dermody, TS, Ouyang, W, Williams, IR, Vijay-Kumar, M & Gewirtz, AT 2014, 'Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18', Science, vol. 346, no. 6211, pp. 861-865. https://doi.org/10.1126/science.1256999

TY - JOUR

T1 - Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18

AU - Zhang, Benyue

AU - Chassaing, Benoit

AU - Shi, Zhenda

AU - Uchiyama, Robin

AU - Zhang, Zhan

AU - Denning, Timothy L.

AU - Crawford, Sue E.

AU - Pruijssers, Andrea J.

AU - Iskarpatyoti, Jason A.

AU - Estes, Mary K.

AU - Dermody, Terence S.

AU - Ouyang, Wenjun

AU - Williams, Ifor R.

AU - Vijay-Kumar, Matam

AU - Gewirtz, Andrew T.

PY - 2014/11/14

Y1 - 2014/11/14

N2 - Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent. Copyright2014 by the American Association for the Advancement of Science; all rights reserved.

AB - Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent. Copyright2014 by the American Association for the Advancement of Science; all rights reserved.

UR - http://www.scopus.com/inward/record.url?scp=84910628469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910628469&partnerID=8YFLogxK

U2 - 10.1126/science.1256999

DO - 10.1126/science.1256999

M3 - Article

C2 - 25395539

AN - SCOPUS:84910628469

SN - 0036-8075

VL - 346

SP - 861

EP - 865

JO - Science

JF - Science

IS - 6211

ER -

Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this