Author
Listed:
- Verena Lütschg
(Institute of Molecular Life Sciences, University of Zurich
Molecular Life Sciences Graduate School, ETH and University of Zurich)
- Karin Boucke
(Institute of Molecular Life Sciences, University of Zurich)
- Silvio Hemmi
(Institute of Molecular Life Sciences, University of Zurich)
- Urs F. Greber
(Institute of Molecular Life Sciences, University of Zurich)
Abstract
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.
Suggested Citation
Verena Lütschg & Karin Boucke & Silvio Hemmi & Urs F. Greber, 2011.
"Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells,"
Nature Communications, Nature, vol. 2(1), pages 1-10, September.
Handle:
RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1391
DOI: 10.1038/ncomms1391
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