Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs
Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, w...
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Format: | Article |
Language: | English |
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Wiley
2015-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2015/281613 |
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author | Karolina Bień Justyna Sokołowska Piotr Bąska Zuzanna Nowak Wanda Stankiewicz Malgorzata Krzyzowska |
author_facet | Karolina Bień Justyna Sokołowska Piotr Bąska Zuzanna Nowak Wanda Stankiewicz Malgorzata Krzyzowska |
author_sort | Karolina Bień |
collection | DOAJ |
description | Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response. |
format | Article |
id | doaj-art-a2e9073af8c94fc89d77e7a104173292 |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2015-01-01 |
publisher | Wiley |
record_format | Article |
series | Mediators of Inflammation |
spelling | doaj-art-a2e9073af8c94fc89d77e7a1041732922025-02-03T05:58:03ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/281613281613Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of LungsKarolina Bień0Justyna Sokołowska1Piotr Bąska2Zuzanna Nowak3Wanda Stankiewicz4Malgorzata Krzyzowska5Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, PolandDepartment of Morphological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, PolandDepartment of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, PolandDepartment of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, PolandMilitary Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, PolandMilitary Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, PolandFas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response.http://dx.doi.org/10.1155/2015/281613 |
spellingShingle | Karolina Bień Justyna Sokołowska Piotr Bąska Zuzanna Nowak Wanda Stankiewicz Malgorzata Krzyzowska Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs Mediators of Inflammation |
title | Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs |
title_full | Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs |
title_fullStr | Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs |
title_full_unstemmed | Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs |
title_short | Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs |
title_sort | fas fasl pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs |
url | http://dx.doi.org/10.1155/2015/281613 |
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