Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut

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Science  18 Mar 2016:
Vol. 351, Issue 6279, pp. 1329-1333
DOI: 10.1126/science.aaf1648

Tuft cells help contain parasites

Trillions of microbes inhabit our guts, including worms and other parasites. Epithelial cells that line the gut orchestrate parasite-targeted immune responses. Howitt et al. now identify a key cellular player in immunity to parasites: tuft cells (see the Perspective by Harris). Tuft cells make up a small fraction of gut epithelial cells but expand when parasites colonize or infect the gut. Parasites cause tuft cells to secrete large amounts of interleukin-25, a key cytokine for parasite clearance that also indirectly feeds back on tuft cells to expand their numbers. Tuft cells express chemosensory signaling machinery: disrupting this blocked parasite-triggered tuft cell expansion and weakened the ability of mice to control a parasitic infection.

Science, this issue p. 1329; see also p. 1264


The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites.

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