Caecal epithelium-derived thymic stromal lymphopoietin is not required for protective immunity against whipworm

Recent research examining classical type two alarmin TSLP has uncovered non-epithelial cellular sources of the cytokine during various murine challenges. Trichuris muris is a key model of type two immunity in the intestine with expulsion being TSLP-dependent. Previous research was suggestive of epithelial production of TSLP in the caecum, but its production during infection has not been characterised in detail. Here, using qPCR, transcript-based imaging, and conditional knockout, we demonstrate caecal epithelium to be a poor source of Tslp, and that non-epithelial upregulation occurs during Trichuris infection, peaking around day 14 post-infection. Conditional knockout of TSLP expression in caecal epithelial cells did not here impact parasite expulsion, but, surprisingly, neutralisation of TSLP from days 15 to 25 produced full susceptibility. These data build on previous work to raise important questions regarding the interaction of TSLP with immunity broadly, as well as the conditions for production of immunity to intestinal helminths.