Intestinal cDC1s provide IL-12 dependent and independent functions required for CD4 + T cell-mediated resistance to Cryptosporidium .

Autor:	Cohn IS; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wallbank BA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Haskins BE; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., O'Dea KM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Pardy RD; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Shaw S; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Merolle MI; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Gullicksrud JA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Christian DA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Striepen B; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hunter CA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 13. Date of Electronic Publication: 2023 Nov 13.
DOI:	10.1101/2023.11.11.566669
Abstrakt:	Cryptosporidium is an enteric pathogen that is a prominent cause of diarrheal disease. Control of this infection requires CD4 + T cells, though the processes that lead to T cell-mediated resistance have been difficult to assess. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to dissect the early events that influence CD4 + T cell priming and effector function. These studies highlight that parasite-specific CD4 + T cells are primed in the draining mesenteric lymph node (mesLN) and differentiate into Th1 cells in the gut, where they mediate IFN-γ-dependent control of the infection. Although type 1 conventional dendritic cells (cDC1s) were not required for initial priming of CD4 + T cells, cDC1s were required for CD4 + T cell expansion and gut homing. cDC1s were also a major source of IL-12 that was not required for priming but promoted full differentiation of CD4 + T cells and local production of IFN-γ. Together, these studies reveal distinct roles for cDC1s in shaping CD4 + T cell responses to enteric infection: first to drive early expansion in the mesLN and second to drive effector responses in the gut. Competing Interests: Competing Interests: J.A.G. is currently affiliated with Cell Press, but all experiments performed by her for these studies were done before she worked there. Therefore, the authors declare no competing interests.
Databáze:	MEDLINE
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