The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis

DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important...

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Autores: Lugo-Villarino, Geanncarlo, Troegeler, Anthony, Balboa, Luciana, Lastrucci, Claire, Duval, Carine, Mercier, Ingrid, Bénard, Alan, Capilla, Florence, Al Saati, Talal, Poincloux, Renaud, Kondova, Ivanela, Verreck, Frank A. W., Cougoule, Céline, Maridonneau-Parini, Isabelle, Sasiain, Maria del Carmen, Neyrolles, Olivier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/42876
Acceso en línea:http://hdl.handle.net/10230/42876
http://dx.doi.org/10.3389/fimmu.2018.01123
Access Level:acceso abierto
Palabra clave:Macrophages
Mycobacterium tuberculosis
DC-SIGN
C-type lectin receptors
Anti-inflammatory
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spelling The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosisLugo-Villarino, GeanncarloTroegeler, AnthonyBalboa, LucianaLastrucci, ClaireDuval, CarineMercier, IngridBénard, AlanCapilla, FlorenceAl Saati, TalalPoincloux, RenaudKondova, IvanelaVerreck, Frank A. W.Cougoule, CélineMaridonneau-Parini, IsabelleSasiain, Maria del CarmenNeyrolles, OlivierMacrophagesMycobacterium tuberculosisDC-SIGNC-type lectin receptorsAnti-inflammatoryDC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb-macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context. First, we demonstrate that DC-SIGN expression is present both in CD68+ macrophages found in tuberculous pulmonary lesions of non-human primates, and in the CD14+ cell population isolated from pleural effusions obtained from TB patients (TB-PE). Likewise, we show that DC-SIGN expression is accentuated in M(IL-4) macrophages derived from peripheral blood CD14+ monocytes isolated from TB patients, or in macrophages stimulated with acellular TB-PE, arguing for the pertinence of DC-SIGN-expressing macrophages in TB. Second, using a siRNA-mediated gene silencing approach, we performed a transcriptomic analysis of DC-SIGN-depleted M(IL-4) macrophages and revealed the upregulation of pro-inflammatory signals in response to challenge with Mtb, as compared to control cells. This pro-inflammatory gene signature was confirmed by RT-qPCR, cytokine/chemokine-based protein array, and ELISA analyses. We also found that inactivation of DC-SIGN renders M(IL-4) macrophages less permissive to Mtb intracellular growth compared to control cells, despite the equal level of bacteria uptake. Last, at the molecular level, we show that DC-SIGN interferes negatively with the pro-inflammatory response and control of Mtb intracellular growth mediated by another CLR, Dectin-1 (CLEC7A). Collectively, this study highlights a dual role for DC-SIGN as, on the one hand, being a host factor granting advantage for Mtb to parasitize macrophages and, on the other hand, representing a molecular switch to turn off the pro-inflammatory response in these cells to prevent potential immunopathology associated to TB.Frontiers201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/42876http://dx.doi.org/10.3389/fimmu.2018.01123reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésFront Immunol. 2018; 9:1123© 2018 Lugo-Villarino, Troegeler, Balboa, Lastrucci, Duval, Mercier, Bénard, Capilla, Al Saati, Poincloux, Kondova, Verreck, Cougoule, Maridonneau-Parini, Sasiain and Neyrolles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/428762026-05-29T05:05:01Z
dc.title.none.fl_str_mv The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
title The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
spellingShingle The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
Lugo-Villarino, Geanncarlo
Macrophages
Mycobacterium tuberculosis
DC-SIGN
C-type lectin receptors
Anti-inflammatory
title_short The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
title_full The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
title_fullStr The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
title_full_unstemmed The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
title_sort The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
dc.creator.none.fl_str_mv Lugo-Villarino, Geanncarlo
Troegeler, Anthony
Balboa, Luciana
Lastrucci, Claire
Duval, Carine
Mercier, Ingrid
Bénard, Alan
Capilla, Florence
Al Saati, Talal
Poincloux, Renaud
Kondova, Ivanela
Verreck, Frank A. W.
Cougoule, Céline
Maridonneau-Parini, Isabelle
Sasiain, Maria del Carmen
Neyrolles, Olivier
author Lugo-Villarino, Geanncarlo
author_facet Lugo-Villarino, Geanncarlo
Troegeler, Anthony
Balboa, Luciana
Lastrucci, Claire
Duval, Carine
Mercier, Ingrid
Bénard, Alan
Capilla, Florence
Al Saati, Talal
Poincloux, Renaud
Kondova, Ivanela
Verreck, Frank A. W.
Cougoule, Céline
Maridonneau-Parini, Isabelle
Sasiain, Maria del Carmen
Neyrolles, Olivier
author_role author
author2 Troegeler, Anthony
Balboa, Luciana
Lastrucci, Claire
Duval, Carine
Mercier, Ingrid
Bénard, Alan
Capilla, Florence
Al Saati, Talal
Poincloux, Renaud
Kondova, Ivanela
Verreck, Frank A. W.
Cougoule, Céline
Maridonneau-Parini, Isabelle
Sasiain, Maria del Carmen
Neyrolles, Olivier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Macrophages
Mycobacterium tuberculosis
DC-SIGN
C-type lectin receptors
Anti-inflammatory
topic Macrophages
Mycobacterium tuberculosis
DC-SIGN
C-type lectin receptors
Anti-inflammatory
description DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb-macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context. First, we demonstrate that DC-SIGN expression is present both in CD68+ macrophages found in tuberculous pulmonary lesions of non-human primates, and in the CD14+ cell population isolated from pleural effusions obtained from TB patients (TB-PE). Likewise, we show that DC-SIGN expression is accentuated in M(IL-4) macrophages derived from peripheral blood CD14+ monocytes isolated from TB patients, or in macrophages stimulated with acellular TB-PE, arguing for the pertinence of DC-SIGN-expressing macrophages in TB. Second, using a siRNA-mediated gene silencing approach, we performed a transcriptomic analysis of DC-SIGN-depleted M(IL-4) macrophages and revealed the upregulation of pro-inflammatory signals in response to challenge with Mtb, as compared to control cells. This pro-inflammatory gene signature was confirmed by RT-qPCR, cytokine/chemokine-based protein array, and ELISA analyses. We also found that inactivation of DC-SIGN renders M(IL-4) macrophages less permissive to Mtb intracellular growth compared to control cells, despite the equal level of bacteria uptake. Last, at the molecular level, we show that DC-SIGN interferes negatively with the pro-inflammatory response and control of Mtb intracellular growth mediated by another CLR, Dectin-1 (CLEC7A). Collectively, this study highlights a dual role for DC-SIGN as, on the one hand, being a host factor granting advantage for Mtb to parasitize macrophages and, on the other hand, representing a molecular switch to turn off the pro-inflammatory response in these cells to prevent potential immunopathology associated to TB.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/42876
http://dx.doi.org/10.3389/fimmu.2018.01123
url http://hdl.handle.net/10230/42876
http://dx.doi.org/10.3389/fimmu.2018.01123
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Front Immunol. 2018; 9:1123
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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