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

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Science  14 Nov 2014:
Vol. 346, Issue 6211, pp. 861-865
DOI: 10.1126/science.1256999

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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.

Flagellin gives rotavirus a one-two punch

Rotavirus causes gastroenteritis, which can be especially severe in infants and young children. The bacterial protein flagellin activates the innate immune system and protects mice against a variety of infectious and inflammatory agents. Zhang et al. now report that flagellin both prevented rotavirus infection in mice and cured mice chronically infected with rotavirus. It did so by activating two distinct innate immune signaling pathways, which led to cells in the infected mice producing the cytokines interleukin 22 and interleukin 18. Similar to flagellin, treating mice with both of these cytokines prevented or cured rotavirus infection.

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