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 journalArticle

90 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)861-865
Number of pages5
JournalScience
Volume346
Issue number6211
DOIs
StatePublished - Nov 14 2014

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Toll-Like Receptor 5
Rotavirus Infections
Flagellin
Interleukin-18
Rotavirus
Interferon Type I
Adaptive Immunity
Innate Immunity
Dendritic Cells
Interferon-gamma
Antiviral Agents
Epithelial Cells
NLR Proteins
interleukin-22
Cytokines
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

Cite this

Zhang, B., Chassaing, B., Shi, Z., Uchiyama, R., Zhang, Z., Denning, T. L., ... 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
Zhang, Benyue ; Chassaing, Benoit ; Shi, Zhenda ; Uchiyama, Robin ; Zhang, Zhan ; Denning, Timothy L. ; Crawford, Sue E. ; Pruijssers, Andrea J. ; Iskarpatyoti, Jason A. ; Estes, Mary K. ; Dermody, Terence S. ; Ouyang, Wenjun ; Williams, Ifor R. ; Kumar, Matam Vijay ; Gewirtz, Andrew T. / Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. In: Science. 2014 ; Vol. 346, No. 6211. pp. 861-865.
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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 Kumar, {Matam Vijay} and Gewirtz, {Andrew T.}",
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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, Kumar, MV & 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

Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. / Zhang, Benyue; Chassaing, Benoit; Shi, Zhenda; Uchiyama, Robin; Zhang, Zhan; Denning, Timothy L.; Crawford, Sue E.; Pruijssers, Andrea J.; Iskarpatyoti, Jason A.; Estes, Mary K.; Dermody, Terence S.; Ouyang, Wenjun; Williams, Ifor R.; Kumar, Matam Vijay; Gewirtz, Andrew T.

In: Science, Vol. 346, No. 6211, 14.11.2014, p. 861-865.

Research output: Contribution to journalArticle

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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 - Kumar, Matam Vijay

AU - Gewirtz, Andrew T.

PY - 2014/11/14

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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.

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Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL et al. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science. 2014 Nov 14;346(6211):861-865. https://doi.org/10.1126/science.1256999