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CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection

The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resul...

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Autores principales: Fischer, Matthew A., Davies, Michael L., Reider, Irene E., Heipertz, Erica L., Epler, Melanie R., Sei, Janet J., Ingersoll, Molly A., Van Rooijen, Nico, Randolph, Gwendalyn J., Norbury, Christopher C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213107/
https://www.ncbi.nlm.nih.gov/pubmed/22102816
http://dx.doi.org/10.1371/journal.ppat.1002374
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author Fischer, Matthew A.
Davies, Michael L.
Reider, Irene E.
Heipertz, Erica L.
Epler, Melanie R.
Sei, Janet J.
Ingersoll, Molly A.
Van Rooijen, Nico
Randolph, Gwendalyn J.
Norbury, Christopher C.
author_facet Fischer, Matthew A.
Davies, Michael L.
Reider, Irene E.
Heipertz, Erica L.
Epler, Melanie R.
Sei, Janet J.
Ingersoll, Molly A.
Van Rooijen, Nico
Randolph, Gwendalyn J.
Norbury, Christopher C.
author_sort Fischer, Matthew A.
collection PubMed
description The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b(+)Ly6C(+)Ly6G(-) monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b(+)Ly6C(+)Ly6G(+) cells. The phenotype of the CD11b(+)Ly6C(+)Ly6G(+) cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b(+)Ly6C(+)Ly6G(+) cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b(+)Ly6C(+)Ly6G(+) cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G(+) cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b(+)Ly6C(+)Ly6G(+) cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction.
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spelling pubmed-32131072011-11-18 CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection Fischer, Matthew A. Davies, Michael L. Reider, Irene E. Heipertz, Erica L. Epler, Melanie R. Sei, Janet J. Ingersoll, Molly A. Van Rooijen, Nico Randolph, Gwendalyn J. Norbury, Christopher C. PLoS Pathog Research Article The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b(+)Ly6C(+)Ly6G(-) monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b(+)Ly6C(+)Ly6G(+) cells. The phenotype of the CD11b(+)Ly6C(+)Ly6G(+) cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b(+)Ly6C(+)Ly6G(+) cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b(+)Ly6C(+)Ly6G(+) cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G(+) cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b(+)Ly6C(+)Ly6G(+) cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction. Public Library of Science 2011-11-10 /pmc/articles/PMC3213107/ /pubmed/22102816 http://dx.doi.org/10.1371/journal.ppat.1002374 Text en Fischer et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fischer, Matthew A.
Davies, Michael L.
Reider, Irene E.
Heipertz, Erica L.
Epler, Melanie R.
Sei, Janet J.
Ingersoll, Molly A.
Van Rooijen, Nico
Randolph, Gwendalyn J.
Norbury, Christopher C.
CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title_full CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title_fullStr CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title_full_unstemmed CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title_short CD11b(+), Ly6G(+) Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection
title_sort cd11b(+), ly6g(+) cells produce type i interferon and exhibit tissue protective properties following peripheral virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213107/
https://www.ncbi.nlm.nih.gov/pubmed/22102816
http://dx.doi.org/10.1371/journal.ppat.1002374
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