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Viral infection. 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.
AuthorsBenyue 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
JournalScience (New York, N.Y.) (Science) Vol. 346 Issue 6211 Pg. 861-5 (Nov 14 2014) ISSN: 1095-9203 [Electronic] United States
PMID25395539 (Publication Type: Journal Article, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014, American Association for the Advancement of Science.
Chemical References
  • Homeodomain Proteins
  • Interleukin-18
  • Interleukins
  • Toll-Like Receptor 5
  • Flagellin
  • RAG-1 protein
  • interleukin-22
Topics
  • Animals
  • Diarrhea (immunology, therapy, virology)
  • Disease Models, Animal
  • Feces (virology)
  • Flagellin (administration & dosage, immunology)
  • Homeodomain Proteins (genetics)
  • Immunity, Innate
  • Interleukin-18 (administration & dosage, genetics, immunology)
  • Interleukins (administration & dosage, genetics, immunology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation
  • Rotavirus Infections (immunology, prevention & control, therapy)
  • Toll-Like Receptor 5 (genetics, physiology)
  • Virus Shedding

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