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

2014; American Association for the Advancement of Science; Volume: 346; Issue: 6211 Linguagem: Inglês

10.1126/science.1256999

1095-9203

Benyue Zhang, Benoît 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,

Pediatric health and respiratory diseases

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.