T helper cell 2 (Th2) responses are required to control multicellular parasitic organisms, which frequently invade the intestine. Dendritic cells (DCs) play an important role in the induction of Th2 responses as they present parasite-derived antigens in the draining lymph nodes and prime naive T cells.
We observed that intestinal Th2 responses against Schistosoma mansoni eggs and Trichuris muris worms did not develop in the absence of IRF4+ DCs. In IRF4f/f CD11c-cre mice we found a significant reduction in the number of CD11b-expressing migrating DCs, which transported parasite antigen to the MLNs. Both, small intestinal (SI) and colonic draining lymph nodes were hereby affected.
Analysis of SI and colonic draining lymph revealed that CD11b+CD103+ DCs were the most numerous population to carry the parasite antigen from the small intestine, whereas CD11b+CD103- DCs carried parasite antigen from the colon. After transfer of purified antigen-carrying DCs into lymph nodes of recipient mice, the populations sufficient to prime Th2 responses in vivo were SI CD11b+CD103+ DCs and colonic CD11b+CD103- DCs.
Thus, different populations of IRF4-dependent DCs promote Th2 responses in the small intestine vs. the colon, revealing hitherto unappreciated functional heterogeneity among intestinal DCs, which could lead to a novel understanding of DC-mediated pathologies in the intestine.