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

TLDR

The intestinal epithelium is a key barrier that must respond to gut protozoa and helminths, yet the mechanisms by which epithelial cells coordinate immunity to these eukaryotes remain poorly understood. We found that tuft cells expand during parasite infection, depend on TRMP5‑mediated chemosensory signaling, produce IL‑25 to drive IL‑13–mediated expansion of tuft cells, goblet cells, eosinophils, and ILC2s, and act as essential sentinels that orchestrate type‑2 immunity against intestinal parasites.

Abstract

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.