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

Science. 2014 Nov 14;346(6211):861-5. doi: 10.1126/science.1256999.

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diarrhea / immunology
  • Diarrhea / therapy
  • Diarrhea / virology
  • Disease Models, Animal
  • Feces / virology
  • Flagellin / administration & dosage*
  • Flagellin / immunology
  • Homeodomain Proteins / genetics
  • Immunity, Innate*
  • Interleukin-18 / administration & dosage
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology*
  • Interleukins / administration & dosage
  • Interleukins / genetics
  • Interleukins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation
  • Rotavirus Infections / immunology
  • Rotavirus Infections / prevention & control*
  • Rotavirus Infections / therapy
  • Toll-Like Receptor 5 / genetics
  • Toll-Like Receptor 5 / physiology*
  • Virus Shedding

Substances

  • Homeodomain Proteins
  • Interleukin-18
  • Interleukins
  • Toll-Like Receptor 5
  • Flagellin
  • RAG-1 protein
  • interleukin-22

Associated data

  • GEO/GSE62479