ArticleImmunity2023
The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells.
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Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- T cell fate is dictated by different antigen-presenting cells in response to dietary versus gut epithelial self-antigen.Immunity · 2026Article
- Beyond Bacteria: The Emerging Role of the Gut Virome and Mycobiome in Celiac Disease.Nutrients · 2026Review
- The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of gut health.Nature reviews. Gastroenterology & hepatology · 2026Article
- Dendritic Cells in the Gastrointestinal System: Division of Labor, Plasticity, and Niche-Specific Adaptation.Immunological reviews · 2026Review
- Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity.Immunity · 2025Article
- Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4＋ T cells.BMB reports · 2025Review
- Is the microbiome important in celiac disease?Journal of the Canadian Association of Gastroenterology · 2025Article
- The renaissance of oral tolerance: merging tradition and new insights.Nature reviews. Immunology · 2025Review
- The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis.Immunity, inflammation and disease · 2024Review
- NRP1 is a receptor for mammalian orthoreovirus engaged by distinct capsid subunits.Cell host & microbe · 2024Article
- Non-Host Factors Influencing Onset and Severity of Celiac Disease.Gastroenterology · 2024Review
- The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy.International journal of molecular sciences · 2023Review
- Celiac disease: mechanisms and emerging therapeutics.Trends in pharmacological sciences · 2023Review
- Protists protecting food tolerance.Trends in immunology · 2023Article
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 3 countries.
Luzmariel Medina SanchezDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Magdalena SillerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yanlin ZengDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; School of Medicine, Tsinghua University, Beijing, China.
Pamela H BriglebGraduate Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Kishan A SanganiDepartment of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA.
Ariadna S SotoDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Clarisse EnglDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Colin R LaughlinDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mohit RanaDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Lauren Van Der KraakDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Surya P PandeyDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mackenzie J BenderDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Britney FitzgeraldDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Lee HeddenDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Kay FiskeInstitute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gwen M TaylorInstitute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Austin P WrightDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA.
Isha D MehtaDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Syed A RahmanDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Systems Immunology, Departments of Immunology and Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Heather J GalipeauFarncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada.
Steven J MullettDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Stacy L GelhausDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Premysl BercikFarncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada.
Timothy J NiceDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA.
Bana JabriDepartment of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA.
Marlies MeiselDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Jishnu DasDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Systems Immunology, Departments of Immunology and Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Terence S DermodyDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Elena F VerdúFarncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada.
Reinhard HinterleitnerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: reinhard@pitt.edu.
University of Pittsburgh · USPopulation Health Research Institute · CAOregon Health & Science University · USUniversity of Chicago · US
Funding
Autoimmunity and Immunopathology Training ProgramT32AI089443 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2010 to 2024
$6.6MUniversity of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1MMedical Scientist National Research Service AwardT32GM150375 · NIGMS · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2023 to 2026
$5.5MViral infections and celiac disease pathogenesisR01DK098435 · NIDDK · UNIVERSITY OF CHICAGO · PI DERMODY, TERENCE S., JABRI, BANA · 2014 to 2022
$5.4MImmunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3MInnate immunity to enteric virus infection by IFN?-stimulated-gene expressionR01AI130055 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Timothy J. Nice · 2017 to 2026
$4.2MRole of gut protists in celiac diseaseR01AI168478 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Reinhard Hinterleitner · 2023 to 2026
$2.3MSystemic immunoregulatory consequences of bacterial translocation during health and diseaseR01DK130897 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MEISEL, MARLIES · 2021 to 2025
$2.2MBringing Untargeted Metabolomics to PittS10OD023402 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GELHAUS, STACY LYNN · 2018 to 2018
$594kGut mucosal type-2 immunity to parasitic infectionsR21AI163721 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HINTERLEITNER, REINHARD · 2021 to 2022
$433kRole of probiotic Lactobacillus reuteri in orchestrating systemic anti-tumor immunityR21CA259636 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MEISEL, MARLIES · 2022 to 2023
$377kFOOD &WATERBORNE DISEASES INTEGRATED RESEARCH NETWORK, ZOONOES RESEAR-N01AI030055 · NIAID · WASHINGTON STATE UNIVERSITY · 2003 to 2003
–NCI NIH HHS R21 CA259636NIAID NIH HHS N01 AI030055NIAID NIH HHS R01 AI130055NIAID NIH HHS R01 AI168478NIAID NIH HHS R21 AI163721NIAID NIH HHS T32 AI060525NIAID NIH HHS T32 AI089443NIDDK NIH HHS R01 DK098435NIDDK NIH HHS R01 DK130897NIGMS NIH HHS R25 GM086262NIGMS NIH HHS T32 GM150375NIH HHS S10 OD023402
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.
Indexed as
AntigensImmunity, InnateAnimalsDendritic CellsDietGlutensHumansImmune ToleranceMiceAntigensGlutensceliac diseasedendritic cellsdietary antigenloss of oral tolerancemicrobiotaoral toleranceregulatory T cellreovirusT helper 1Tritrichomonas
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