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. Galipeau; Steven 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

doi:10.1016/j.immuni.2023.06.022

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

Molecular Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

4 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 language	English (US)
Pages (from-to)	1862-1875.e9
Journal	Immunity
Volume	56
Issue number	8
DOIs	https://doi.org/10.1016/j.immuni.2023.06.022
State	Published - Aug 8 2023

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2023.06.022

Cite this

Medina Sanchez, L., Siller, M., Zeng, Y., Brigleb, P. H., Sangani, K. A., Soto, A. S., Engl, C., Laughlin, C. R., Rana, M., Van Der Kraak, L., Pandey, S. P., Bender, M. J., Fitzgerald, B., Hedden, L., Fiske, K., Taylor, G. M., Wright, A. P., Mehta, I. D., Rahman, S. A., ... Hinterleitner, R. (2023). The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells. Immunity, 56(8), 1862-1875.e9. https://doi.org/10.1016/j.immuni.2023.06.022

Medina Sanchez, L, Siller, M, Zeng, Y, Brigleb, PH, Sangani, KA, Soto, AS, Engl, C, Laughlin, CR, Rana, M, Van Der Kraak, L, Pandey, SP, Bender, MJ, Fitzgerald, B, Hedden, L, Fiske, K, Taylor, GM, Wright, AP, Mehta, ID, Rahman, SA, Galipeau, HJ, Mullett, SJ, Gelhaus, SL, Watkins, SC, Bercik, P, Nice, TJ, Jabri, B, Meisel, M, Das, J, Dermody, TS, Verdú, EF & Hinterleitner, R 2023, 'The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells', Immunity, vol. 56, no. 8, pp. 1862-1875.e9. https://doi.org/10.1016/j.immuni.2023.06.022

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

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.",

keywords = "T helper 1, Tritrichomonas, celiac disease, dendritic cells, dietary antigen, loss of oral tolerance, microbiota, oral tolerance, regulatory T cell, reovirus",

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

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doi = "10.1016/j.immuni.2023.06.022",

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T1 - The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells

AU - Medina Sanchez, Luzmariel

AU - Siller, Magdalena

AU - Zeng, Yanlin

AU - Brigleb, Pamela H.

AU - Sangani, Kishan A.

AU - Soto, Ariadna S.

AU - Engl, Clarisse

AU - Laughlin, Colin R.

AU - Rana, Mohit

AU - Van Der Kraak, Lauren

AU - Pandey, Surya P.

AU - Bender, Mackenzie J.

AU - Fitzgerald, Britney

AU - Hedden, Lee

AU - Fiske, Kay

AU - Taylor, Gwen M.

AU - Wright, Austin P.

AU - Mehta, Isha D.

AU - Rahman, Syed A.

AU - Galipeau, Heather J.

AU - Mullett, Steven J.

AU - Gelhaus, Stacy L.

AU - Watkins, Simon C.

AU - Bercik, Premysl

AU - Nice, Timothy J.

AU - Jabri, Bana

AU - Meisel, Marlies

AU - Das, Jishnu

AU - Dermody, Terence S.

AU - Verdú, Elena F.

AU - Hinterleitner, Reinhard

PY - 2023/8/8

Y1 - 2023/8/8

N2 - 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.

AB - 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.

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KW - Tritrichomonas

KW - celiac disease

KW - dendritic cells

KW - dietary antigen

KW - loss of oral tolerance

KW - microbiota

KW - oral tolerance

KW - regulatory T cell

KW - reovirus

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DO - 10.1016/j.immuni.2023.06.022

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AN - SCOPUS:85166549809

SN - 1074-7613

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SP - 1862-1875.e9

JO - Immunity

JF - Immunity

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ER -

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

Abstract

Keywords

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