Immunity to Trichuris muris infection is unimpacted by epithelial knockout of TSLP expression. Imaging of transcription in the caecum reveals Tslp transcription throughout infection in EpCAM-, Foxl1-, Ccl24- lamina propria-resident cells, contributing during the expulsion phase of infection.
ABSTRACT
Recent research examining classical type two alarmin TSLP has uncovered non-epithelial cellular sources of the cytokine in various murine challenges. Trichuris muris is a key model of type two immunity in the intestine, with expulsion being TSLP-dependent. Previous research has indicated epithelial production of TSLP in the caecum, but its production during infection has not been characterised in detail. Here, conditional knockout of Tslp expression in caecal epithelial cells was shown not to impact parasite expulsion, but, surprisingly, neutralisation of TSLP from days 15 to 25 post-infection produced full susceptibility. qPCR and transcript-based imaging were used to demonstrate that caecal epithelium is a poor source of Tslp, and non-epithelial Tslp expression is observed during Trichuris infection in EpCAM-negative cells. These data build on previous work to raise important questions regarding the interaction of TSLP with immunity broadly, as well as the conditions for the production of immunity to intestinal helminths.