A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.

Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analys...

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Autores principales:	Gennady Bocharov, Roland Züst, Luisa Cervantes-Barragan, Tatyana Luzyanina, Egor Chiglintsev, Valery A Chereshnev, Volker Thiel, Burkhard Ludewig
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/17664e4d4c604b49b97572a066cc6e6a
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spelling	oai:doaj.org-article:17664e4d4c604b49b97572a066cc6e6a2021-12-02T20:00:27ZA systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.1553-73661553-737410.1371/journal.ppat.1001017https://doaj.org/article/17664e4d4c604b49b97572a066cc6e6a2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20661432/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mphis). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3) to 10(4) Mphis from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a 'sink' for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.Gennady BocharovRoland ZüstLuisa Cervantes-BarraganTatyana LuzyaninaEgor ChiglintsevValery A ChereshnevVolker ThielBurkhard LudewigPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 7, p e1001017 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Gennady Bocharov Roland Züst Luisa Cervantes-Barragan Tatyana Luzyanina Egor Chiglintsev Valery A Chereshnev Volker Thiel Burkhard Ludewig A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
description	Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mphis). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3) to 10(4) Mphis from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a 'sink' for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.
format	article
author	Gennady Bocharov Roland Züst Luisa Cervantes-Barragan Tatyana Luzyanina Egor Chiglintsev Valery A Chereshnev Volker Thiel Burkhard Ludewig
author_facet	Gennady Bocharov Roland Züst Luisa Cervantes-Barragan Tatyana Luzyanina Egor Chiglintsev Valery A Chereshnev Volker Thiel Burkhard Ludewig
author_sort	Gennady Bocharov
title	A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
title_short	A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
title_full	A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
title_fullStr	A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
title_full_unstemmed	A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
title_sort	systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/17664e4d4c604b49b97572a066cc6e6a
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A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.

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