Abstract

Cryptosporidium is an enteric pathogen and a prominent cause of diarrheal disease worldwide. Control of Cryptosporidium requires CD4+ T cells, but how protective CD4+ T cell responses are generated is poorly understood. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to understand the basis for CD4+ T cell priming and effector function. These studies revealed that parasite-specific CD4+ T cells are primed in the draining mesenteric lymph node but differentiate into Th1 cells in the gut to provide local parasite control. Although type 1 conventional dendritic cells (cDC1s) were dispensable for CD4+ T cell priming, they were required for CD4+ T cell gut homing and were a source of IL-12 at the site of infection that promoted local production of IFN-γ. Thus, cDC1s have distinct roles in shaping CD4+ T cell responses to an enteric infection: first, to promote gut homing from the mesLN, and second, to drive effector responses in the intestine.

MeSH

Infections, Parasites, Cells, T-Lymphocytes, Interleukin-12, Cues

Cited by

• Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-γ on parasite restriction. PLoS Pathog, 2024
• De-coupling immune parameters and toxicity associated with IL-12 agonism. Cell Rep, 2025
• Evaluating the Effects of Viruses on Eastern Indigo Snakes (Drymarchon couperi) with Gastric Cryptosporidiosis. Viruses, 2024
• Promising efficacy of nitrogen-containing bisphosphonates against the infection of Cryptosporidium spp. Int J Parasitol Drugs Drug Resist, 2025