Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repr...

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Autores principales:	Daniel Schnepf, Pedro Hernandez, Tanel Mahlakõiv, Stefania Crotta, Meagan E Sullender, Stefan T Peterson, Annette Ohnemus, Camille Michiels, Ian Gentle, Laure Dumoutier, Celso A Reis, Andreas Diefenbach, Andreas Wack, Megan T Baldridge, Peter Staeheli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d68b02450db24632b3ba2774fe30dfac
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spelling	oai:doaj.org-article:d68b02450db24632b3ba2774fe30dfac2021-12-02T20:15:02ZRotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.1932-620310.1371/journal.pone.0247738https://doaj.org/article/d68b02450db24632b3ba2774fe30dfac2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0247738https://doaj.org/toc/1932-6203The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive.Daniel SchnepfPedro HernandezTanel MahlakõivStefania CrottaMeagan E SullenderStefan T PetersonAnnette OhnemusCamille MichielsIan GentleLaure DumoutierCelso A ReisAndreas DiefenbachAndreas WackMegan T BaldridgePeter StaeheliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0247738 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Schnepf Pedro Hernandez Tanel Mahlakõiv Stefania Crotta Meagan E Sullender Stefan T Peterson Annette Ohnemus Camille Michiels Ian Gentle Laure Dumoutier Celso A Reis Andreas Diefenbach Andreas Wack Megan T Baldridge Peter Staeheli Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
description	The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive.
format	article
author	Daniel Schnepf Pedro Hernandez Tanel Mahlakõiv Stefania Crotta Meagan E Sullender Stefan T Peterson Annette Ohnemus Camille Michiels Ian Gentle Laure Dumoutier Celso A Reis Andreas Diefenbach Andreas Wack Megan T Baldridge Peter Staeheli
author_facet	Daniel Schnepf Pedro Hernandez Tanel Mahlakõiv Stefania Crotta Meagan E Sullender Stefan T Peterson Annette Ohnemus Camille Michiels Ian Gentle Laure Dumoutier Celso A Reis Andreas Diefenbach Andreas Wack Megan T Baldridge Peter Staeheli
author_sort	Daniel Schnepf
title	Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
title_short	Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
title_full	Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
title_fullStr	Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
title_full_unstemmed	Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
title_sort	rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d68b02450db24632b3ba2774fe30dfac
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Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.

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