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Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells
Type I interferons (IFN-I) are antiviral cytokines that signal through the ubiquitous IFN-I receptor (IFNAR). Following footpad infection with ectromelia virus (ECTV), a mouse-specific pathogen, C57BL/6 (B6) mice survive without disease, while B6 mice broadly deficient in IFNAR succumb rapidly. We n...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172060/ https://www.ncbi.nlm.nih.gov/pubmed/34015056 http://dx.doi.org/10.1371/journal.ppat.1009593 |
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author | Melo-Silva, Carolina R. Alves-Peixoto, Pedro Heath, Natasha Tang, Lingjuan Montoya, Brian Knudson, Cory J. Stotesbury, Colby Ferez, Maria Wong, Eric Sigal, Luis J. |
author_facet | Melo-Silva, Carolina R. Alves-Peixoto, Pedro Heath, Natasha Tang, Lingjuan Montoya, Brian Knudson, Cory J. Stotesbury, Colby Ferez, Maria Wong, Eric Sigal, Luis J. |
author_sort | Melo-Silva, Carolina R. |
collection | PubMed |
description | Type I interferons (IFN-I) are antiviral cytokines that signal through the ubiquitous IFN-I receptor (IFNAR). Following footpad infection with ectromelia virus (ECTV), a mouse-specific pathogen, C57BL/6 (B6) mice survive without disease, while B6 mice broadly deficient in IFNAR succumb rapidly. We now show that for survival to ECTV, only hematopoietic cells require IFNAR expression. Survival to ECTV specifically requires IFNAR in both natural killer (NK) cells and monocytes. However, intrinsic IFNAR signaling is not essential for adaptive immune cell responses or to directly protect non-hematopoietic cells such as hepatocytes, which are principal ECTV targets. Mechanistically, IFNAR-deficient NK cells have reduced cytolytic function, while lack of IFNAR in monocytes dampens IFN-I production and hastens virus dissemination. Thus, during a pathogenic viral infection, IFN-I coordinates innate immunity by stimulating monocytes in a positive feedback loop and by inducing NK cell cytolytic function. |
format | Online Article Text |
id | pubmed-8172060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-81720602021-06-14 Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells Melo-Silva, Carolina R. Alves-Peixoto, Pedro Heath, Natasha Tang, Lingjuan Montoya, Brian Knudson, Cory J. Stotesbury, Colby Ferez, Maria Wong, Eric Sigal, Luis J. PLoS Pathog Research Article Type I interferons (IFN-I) are antiviral cytokines that signal through the ubiquitous IFN-I receptor (IFNAR). Following footpad infection with ectromelia virus (ECTV), a mouse-specific pathogen, C57BL/6 (B6) mice survive without disease, while B6 mice broadly deficient in IFNAR succumb rapidly. We now show that for survival to ECTV, only hematopoietic cells require IFNAR expression. Survival to ECTV specifically requires IFNAR in both natural killer (NK) cells and monocytes. However, intrinsic IFNAR signaling is not essential for adaptive immune cell responses or to directly protect non-hematopoietic cells such as hepatocytes, which are principal ECTV targets. Mechanistically, IFNAR-deficient NK cells have reduced cytolytic function, while lack of IFNAR in monocytes dampens IFN-I production and hastens virus dissemination. Thus, during a pathogenic viral infection, IFN-I coordinates innate immunity by stimulating monocytes in a positive feedback loop and by inducing NK cell cytolytic function. Public Library of Science 2021-05-20 /pmc/articles/PMC8172060/ /pubmed/34015056 http://dx.doi.org/10.1371/journal.ppat.1009593 Text en © 2021 Melo-Silva et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Melo-Silva, Carolina R. Alves-Peixoto, Pedro Heath, Natasha Tang, Lingjuan Montoya, Brian Knudson, Cory J. Stotesbury, Colby Ferez, Maria Wong, Eric Sigal, Luis J. Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title | Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title_full | Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title_fullStr | Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title_full_unstemmed | Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title_short | Resistance to lethal ectromelia virus infection requires Type I interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
title_sort | resistance to lethal ectromelia virus infection requires type i interferon receptor in natural killer cells and monocytes but not in adaptive immune or parenchymal cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172060/ https://www.ncbi.nlm.nih.gov/pubmed/34015056 http://dx.doi.org/10.1371/journal.ppat.1009593 |
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