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 journalArticlepeer-review

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

All Science Journal Classification (ASJC) codes

  • General

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