Intestinal cDC1s provide cues required for CD4+ T cell-mediated resistance to Cryptosporidium

• Published in: The Journal of experimental medicine Vol. 221; no. 7
• Main Authors: Cohn, Ian S, Wallbank, Bethan A, Haskins, Breanne E, O'Dea, Keenan M, Pardy, Ryan D, Shaw, Sebastian, Merolle, Maria I, Gullicksrud, Jodi A, Christian, David A, Striepen, Boris, Hunter, Christopher A
• Format: Journal Article
• Language: English
• Published: United States 01.07.2024
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - parasitology; Cryptosporidiosis - immunology; Cryptosporidiosis - parasitology; Cryptosporidium - immunology; Cryptosporidium - physiology; Dendritic Cells - immunology; Dendritic Cells - parasitology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-12 - immunology; Interleukin-12 - metabolism; Intestines - immunology; Intestines - parasitology; Lymph Nodes - immunology; Lymph Nodes - parasitology; Mice; Mice, Inbred C57BL; Th1 Cells - immunology
• ISSN: 1540-9538
• DOI: 10.1084/jem.20232067

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.