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.
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Authors | 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 |
Journal | Science (New York, N.Y.)
(Science)
Vol. 346
Issue 6211
Pg. 861-5
(Nov 14 2014)
ISSN: 1095-9203 [Electronic] United States |
PMID | 25395539
(Publication Type: Journal Article, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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