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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1862-1875.e9
JournalImmunity
Volume56
Issue number8
DOIs
StatePublished - 8 Aug 2023
Externally publishedYes

Keywords

  • T helper 1
  • Tritrichomonas
  • celiac disease
  • dendritic cells
  • dietary antigen
  • loss of oral tolerance
  • microbiota
  • oral tolerance
  • regulatory T cell
  • reovirus

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