Identification of antigen-presenting cell-T cell interactions driving immune responses to food

The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4+ T cells and inducing their differentiation into regulatory (pTreg) or inflammatory (Th) subsets. Here, we used LIPSTIC to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions. We show that helminth infections disrupted tolerance proportionally to the reduction in ratio between tolerogenic, including migratory cDC1s and Rorγt+ APCs, and inflammatory APCs, represented primarily by cDC2 subsets. However, the inflammatory subset of cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific TH2 cell differentiation. Our data uncover cellular mechanisms by which tolerance to food is induced and can be disrupted by infection. DCs from duodenal gut-draining lymph nodes (D-gLNs) of mice under steady-state and helminth-infected conditions were analyzed by bulk RNA-seq. Single-cell RNA-seq (SmartSeq2) was performed on individual DCs from D-gLNs of steady-state and helminth-infected mice. DCs from the lamina propria of the duodenum in steady-state and helminth-infected mice were analyzed using 10x Genomics single-cell RNA-seq.