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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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247738&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-d68b02450db24632b3ba2774fe30dfac |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d68b02450db24632b3ba2774fe30dfac2025-08-20T03:25:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01168e024773810.1371/journal.pone.0247738Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.Daniel SchnepfPedro HernandezTanel MahlakõivStefania CrottaMeagan E SullenderStefan T PetersonAnnette OhnemusCamille MichielsIan GentleLaure DumoutierCelso A ReisAndreas DiefenbachAndreas WackMegan T BaldridgePeter StaeheliThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247738&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247738&type=printable |
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