Flagellin is the main microbe-associated motif recognized in the gut, and this is mediated by the host sensor molecules TLR5 and NLRC4. In Science, Gewirtz and colleagues harness the flagellin-recognition pathway to enhance resistance in a mouse model of rotavirus infection. The administration of flagellin before a high infectious dose of rotavirus results in considerable resistance to infection even in RAG recombinase–deficient mice, which completely lack adaptive immunity, or mice that lack interferon signaling. This resistance is mediated instead by dendritic cells that produce the proinflammatory cytokines IL-12, IL-18 and IL-23 in response to flagellin. These cytokines have two main effects: first, to drive the activation of innate lymphoid cells, and second, to induce the apoptosis of intestinal epithelial cells, which robs rotavirus of its reproductive niche. Activated innate lymphoid cells in turn release IL-22, which elicits an antiviral gene-expression program in intestinal epithelial cells. Stimulation of innate immunity may therefore be potentially effective in diverse infections.

Science 346, 861–865 (2014)