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The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells

2023; Cell Press; Volume: 56; Issue: 8 Linguagem: Inglês

10.1016/j.immuni.2023.06.022

1097-4180

Luzmariel Medina Sanchez, Magdalena Siller, Yanlin Zeng, Pamela H. Brigleb, Kishan Sangani, Ariadna S. Soto, Clarisse Engl, Colin R. Laughlin, Mohit Rana, Lauren Van Der Kraak, Surya Prakash Pandey, Mackenzie Bender, Britney Fitzgerald, Lee Hedden, Kay L. Fiske, Gwen M. Taylor, Austin P Wright, Isha Mehta, Syed A. Rahman, Heather J. Galipeau, Steven J. Mullett, Stacy L. Gelhaus, Simon C. Watkins, Přemysl Berčík, Timothy J. Nice, Bana Jabrì, Marlies Meisel, Jishnu Das, Terence S. Dermody, Elena F. Verdú, Reinhard Hinterleitner,

Transgenic Plants and Applications

Summary Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus- and murine norovirus-mediated LOT, independent of the microbiota. Protection was not attributable to antiviral host responses or T. arnold -mediated innate type 2 immunity. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs, subsequently limiting Th1 and promoting regulatory T cell responses. Finally, analysis of fecal microbiomes showed that T. arnold- related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings will motivate further exploration of oral-tolerance-promoting protists in CeD and other immune-mediated food sensitivities.