The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620986
Title:
The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion.
Authors:
Zischke, Jasmin; Mamareli, Panagiota; Pokoyski, Claudia; Gabaev, Ildar; Buyny, Sabine; Jacobs, Roland; Falk, Christine S; Lochner, Matthias; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Schulz, Thomas F; Kay-Fedorov, Penelope C
Abstract:
Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus. The mechanisms by which HCMV affects T cell IL-10 secretion are not understood. We show here that treatment of PBMC with purified pUL11 induces IL-10 producing T cells as a result of pUL11 binding to the CD45 phosphatase on T cells. IL-10 production induced by HCMV infection is also in part mediated by pUL11. Supernatants from pUL11 treated cells have anti-inflammatory effects on untreated PBMC. Considering the mechanism, CD45 can be a positive or negative regulator of TCR signalling, depending on its expression level, and we show that pUL11 also has concentration dependent activating or inhibitory effects on T cell proliferation and on the kinase function of the CD45 substrate Lck. pUL11 is therefore the first example of a viral protein that can target CD45 to induce T cells with anti-inflammatory properties. It is also the first HCMV protein shown to induce T cell IL-10 secretion. Understanding the mechanisms by which pUL11-induced changes in signal strength influence T cell development and function may provide the basis for the development of novel antiviral treatments and therapies against immune pathologies.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Citation:
The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion. 2017, 13 (6):e1006454 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Jun-2017
URI:
http://hdl.handle.net/10033/620986
DOI:
10.1371/journal.ppat.1006454
PubMed ID:
28628650
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorZischke, Jasminen
dc.contributor.authorMamareli, Panagiotaen
dc.contributor.authorPokoyski, Claudiaen
dc.contributor.authorGabaev, Ildaren
dc.contributor.authorBuyny, Sabineen
dc.contributor.authorJacobs, Rolanden
dc.contributor.authorFalk, Christine Sen
dc.contributor.authorLochner, Matthiasen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorSchulz, Thomas Fen
dc.contributor.authorKay-Fedorov, Penelope Cen
dc.date.accessioned2017-07-04T13:09:31Z-
dc.date.available2017-07-04T13:09:31Z-
dc.date.issued2017-06-
dc.identifier.citationThe human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion. 2017, 13 (6):e1006454 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid28628650-
dc.identifier.doi10.1371/journal.ppat.1006454-
dc.identifier.urihttp://hdl.handle.net/10033/620986-
dc.description.abstractHuman Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus. The mechanisms by which HCMV affects T cell IL-10 secretion are not understood. We show here that treatment of PBMC with purified pUL11 induces IL-10 producing T cells as a result of pUL11 binding to the CD45 phosphatase on T cells. IL-10 production induced by HCMV infection is also in part mediated by pUL11. Supernatants from pUL11 treated cells have anti-inflammatory effects on untreated PBMC. Considering the mechanism, CD45 can be a positive or negative regulator of TCR signalling, depending on its expression level, and we show that pUL11 also has concentration dependent activating or inhibitory effects on T cell proliferation and on the kinase function of the CD45 substrate Lck. pUL11 is therefore the first example of a viral protein that can target CD45 to induce T cells with anti-inflammatory properties. It is also the first HCMV protein shown to induce T cell IL-10 secretion. Understanding the mechanisms by which pUL11-induced changes in signal strength influence T cell development and function may provide the basis for the development of novel antiviral treatments and therapies against immune pathologies.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.