Cargando…
Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells
Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the lu...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091692/ https://www.ncbi.nlm.nih.gov/pubmed/21750545 http://dx.doi.org/10.1038/ncomms1391 |
_version_ | 1783510047783911424 |
---|---|
author | Lütschg, Verena Boucke, Karin Hemmi, Silvio Greber, Urs F. |
author_facet | Lütschg, Verena Boucke, Karin Hemmi, Silvio Greber, Urs F. |
author_sort | Lütschg, Verena |
collection | PubMed |
description | Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a Src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms1391) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7091692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70916922020-03-24 Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells Lütschg, Verena Boucke, Karin Hemmi, Silvio Greber, Urs F. Nat Commun Article Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a Src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms1391) contains supplementary material, which is available to authorized users. Nature Publishing Group UK 2011-07-12 /pmc/articles/PMC7091692/ /pubmed/21750545 http://dx.doi.org/10.1038/ncomms1391 Text en © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2011 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Article Lütschg, Verena Boucke, Karin Hemmi, Silvio Greber, Urs F. Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title | Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title_full | Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title_fullStr | Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title_full_unstemmed | Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title_short | Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
title_sort | chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091692/ https://www.ncbi.nlm.nih.gov/pubmed/21750545 http://dx.doi.org/10.1038/ncomms1391 |
work_keys_str_mv | AT lutschgverena chemotacticantiviralcytokinespromoteinfectiousapicalentryofhumanadenovirusintopolarizedepithelialcells AT bouckekarin chemotacticantiviralcytokinespromoteinfectiousapicalentryofhumanadenovirusintopolarizedepithelialcells AT hemmisilvio chemotacticantiviralcytokinespromoteinfectiousapicalentryofhumanadenovirusintopolarizedepithelialcells AT greberursf chemotacticantiviralcytokinespromoteinfectiousapicalentryofhumanadenovirusintopolarizedepithelialcells |