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Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection

The pathogenesis of viral infections involves an immune response by cytokines, causing a deleterious effect on organ function, in addition to tissue destruction due to viral replication. Clinical symptoms and laboratory findings of the human coronavirus disease COVID-19, caused by the novel coronavi...

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Autores principales: Lavi, Ehud, Cong, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245307/
https://www.ncbi.nlm.nih.gov/pubmed/32454103
http://dx.doi.org/10.1016/j.yexmp.2020.104474
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author Lavi, Ehud
Cong, Lin
author_facet Lavi, Ehud
Cong, Lin
author_sort Lavi, Ehud
collection PubMed
description The pathogenesis of viral infections involves an immune response by cytokines, causing a deleterious effect on organ function, in addition to tissue destruction due to viral replication. Clinical symptoms and laboratory findings of the human coronavirus disease COVID-19, caused by the novel coronavirus SARS CoV-2, indicate cytokine involvement. Our laboratory showed that an experimental murine coronavirus (MHV-A59) can be transmitted into the brain by intranasal or intracerebral exposure and that neurovirulence is mediated by cytokine secretion. In this study we investigated which cells in the brain produce cytokines, thus functioning as the brain's innate immune system. Using tissue cultures of microglia, and clonal populations of astrocytes, we found that microglia and type I astrocytes (but not types II and III), produced pro-inflammatory cytokines in response to MHV-A59 infection. A molecularly closely related, non-encephalitic strain of the virus (MHV-2) caused in vitro infection, but without cytokine induction. Furthermore, immunofluorescence and immunohistochemistry revealed that type I astrocytes and microglia have perivascular foot processes necessary for the formation of the perivascular glymphatic system, the anatomical site of the brain's innate immune system. Cytokine secretion by type I astrocytes and microglia, as part of the brain's glymphatic and innate immune system, contributes to the pathogenesis of an encephalitic coronavirus infection, and indicates the rationale for anti-cytokine therapies for COVID-19.
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spelling pubmed-72453072020-05-26 Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection Lavi, Ehud Cong, Lin Exp Mol Pathol Article The pathogenesis of viral infections involves an immune response by cytokines, causing a deleterious effect on organ function, in addition to tissue destruction due to viral replication. Clinical symptoms and laboratory findings of the human coronavirus disease COVID-19, caused by the novel coronavirus SARS CoV-2, indicate cytokine involvement. Our laboratory showed that an experimental murine coronavirus (MHV-A59) can be transmitted into the brain by intranasal or intracerebral exposure and that neurovirulence is mediated by cytokine secretion. In this study we investigated which cells in the brain produce cytokines, thus functioning as the brain's innate immune system. Using tissue cultures of microglia, and clonal populations of astrocytes, we found that microglia and type I astrocytes (but not types II and III), produced pro-inflammatory cytokines in response to MHV-A59 infection. A molecularly closely related, non-encephalitic strain of the virus (MHV-2) caused in vitro infection, but without cytokine induction. Furthermore, immunofluorescence and immunohistochemistry revealed that type I astrocytes and microglia have perivascular foot processes necessary for the formation of the perivascular glymphatic system, the anatomical site of the brain's innate immune system. Cytokine secretion by type I astrocytes and microglia, as part of the brain's glymphatic and innate immune system, contributes to the pathogenesis of an encephalitic coronavirus infection, and indicates the rationale for anti-cytokine therapies for COVID-19. Elsevier Inc. 2020-08 2020-05-23 /pmc/articles/PMC7245307/ /pubmed/32454103 http://dx.doi.org/10.1016/j.yexmp.2020.104474 Text en © 2020 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Lavi, Ehud
Cong, Lin
Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title_full Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title_fullStr Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title_full_unstemmed Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title_short Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
title_sort type i astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245307/
https://www.ncbi.nlm.nih.gov/pubmed/32454103
http://dx.doi.org/10.1016/j.yexmp.2020.104474
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