Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses

Helminth parasite infections of humans and livestock are a global health and economic problem. Resistance of helminths to current drug treatment is an increasing problem and alternative control approaches, including vaccines, are needed. Effective vaccine design requires knowledge of host immune mec...

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Autores principales:	Katie A. Hildersley, Tom N. McNeilly, Victoria Gillan, Thomas D. Otto, Stephan Löser, François Gerbe, Philippe Jay, Rick M. Maizels, Eileen Devaney, Collette Britton
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Tuft cell parasitic nematode immunity gastrointestinal tract single cell RNA sequencing RNAscope Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/3d47635cf36f42a0a19214acb01c4e0c
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spelling	oai:doaj.org-article:3d47635cf36f42a0a19214acb01c4e0c2021-11-22T07:25:06ZTuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses1664-322410.3389/fimmu.2021.781108https://doaj.org/article/3d47635cf36f42a0a19214acb01c4e0c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.781108/fullhttps://doaj.org/toc/1664-3224Helminth parasite infections of humans and livestock are a global health and economic problem. Resistance of helminths to current drug treatment is an increasing problem and alternative control approaches, including vaccines, are needed. Effective vaccine design requires knowledge of host immune mechanisms and how these are stimulated. Mouse models of helminth infection indicate that tuft cells, an unusual type of epithelial cell, may ‘sense’ infection in the small intestine and trigger a type 2 immune response. Currently nothing is known of tuft cells in immunity in other host species and in other compartments of the gastrointestinal (GI) tract. Here we address this gap and use immunohistochemistry and single cell RNA-sequencing to detail the presence and gene expression profile of tuft cells in sheep following nematode infections. We identify and characterize tuft cells in the ovine abomasum (true stomach of ruminants) and show that they increase significantly in number following infection with the globally important nematodes Teladorsagia circumcincta and Haemonchus contortus. Ovine abomasal tuft cells show enriched expression of tuft cell markers POU2F3, GFI1B, TRPM5 and genes involved in signaling and inflammatory pathways. However succinate receptor SUCNR1 and free fatty acid receptor FFAR3, proposed as ‘sensing’ receptors in murine tuft cells, are not expressed, and instead ovine tuft cells are enriched for taste receptor TAS2R16 and mechanosensory receptor ADGRG6. We also identify tuft cell sub-clusters at potentially different stages of maturation, suggesting a dynamic process not apparent from mouse models of infection. Our findings reveal a tuft cell response to economically important parasite infections and show that while tuft cell effector functions have been retained during mammalian evolution, receptor specificity has diverged. Our data advance knowledge of host-parasite interactions in the GI mucosa and identify receptors that may potentiate type 2 immunity for optimized control of parasitic nematodes.Katie A. HildersleyKatie A. HildersleyTom N. McNeillyVictoria GillanThomas D. OttoStephan LöserFrançois GerbePhilippe JayRick M. MaizelsEileen DevaneyCollette BrittonFrontiers Media S.A.articleTuft cellparasitic nematodeimmunitygastrointestinal tractsingle cell RNA sequencingRNAscopeImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tuft cell parasitic nematode immunity gastrointestinal tract single cell RNA sequencing RNAscope Immunologic diseases. Allergy RC581-607
spellingShingle	Tuft cell parasitic nematode immunity gastrointestinal tract single cell RNA sequencing RNAscope Immunologic diseases. Allergy RC581-607 Katie A. Hildersley Katie A. Hildersley Tom N. McNeilly Victoria Gillan Thomas D. Otto Stephan Löser François Gerbe Philippe Jay Rick M. Maizels Eileen Devaney Collette Britton Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
description	Helminth parasite infections of humans and livestock are a global health and economic problem. Resistance of helminths to current drug treatment is an increasing problem and alternative control approaches, including vaccines, are needed. Effective vaccine design requires knowledge of host immune mechanisms and how these are stimulated. Mouse models of helminth infection indicate that tuft cells, an unusual type of epithelial cell, may ‘sense’ infection in the small intestine and trigger a type 2 immune response. Currently nothing is known of tuft cells in immunity in other host species and in other compartments of the gastrointestinal (GI) tract. Here we address this gap and use immunohistochemistry and single cell RNA-sequencing to detail the presence and gene expression profile of tuft cells in sheep following nematode infections. We identify and characterize tuft cells in the ovine abomasum (true stomach of ruminants) and show that they increase significantly in number following infection with the globally important nematodes Teladorsagia circumcincta and Haemonchus contortus. Ovine abomasal tuft cells show enriched expression of tuft cell markers POU2F3, GFI1B, TRPM5 and genes involved in signaling and inflammatory pathways. However succinate receptor SUCNR1 and free fatty acid receptor FFAR3, proposed as ‘sensing’ receptors in murine tuft cells, are not expressed, and instead ovine tuft cells are enriched for taste receptor TAS2R16 and mechanosensory receptor ADGRG6. We also identify tuft cell sub-clusters at potentially different stages of maturation, suggesting a dynamic process not apparent from mouse models of infection. Our findings reveal a tuft cell response to economically important parasite infections and show that while tuft cell effector functions have been retained during mammalian evolution, receptor specificity has diverged. Our data advance knowledge of host-parasite interactions in the GI mucosa and identify receptors that may potentiate type 2 immunity for optimized control of parasitic nematodes.
format	article
author	Katie A. Hildersley Katie A. Hildersley Tom N. McNeilly Victoria Gillan Thomas D. Otto Stephan Löser François Gerbe Philippe Jay Rick M. Maizels Eileen Devaney Collette Britton
author_facet	Katie A. Hildersley Katie A. Hildersley Tom N. McNeilly Victoria Gillan Thomas D. Otto Stephan Löser François Gerbe Philippe Jay Rick M. Maizels Eileen Devaney Collette Britton
author_sort	Katie A. Hildersley
title	Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
title_short	Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
title_full	Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
title_fullStr	Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
title_full_unstemmed	Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
title_sort	tuft cells increase following ovine intestinal parasite infections and define evolutionarily conserved and divergent responses
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3d47635cf36f42a0a19214acb01c4e0c
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Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses

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