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; 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

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

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dc.contributor.author Lugo-Villarino, Geanncarlo
dc.contributor.author Troegeler, Anthony
dc.contributor.author Balboa, Luciana
dc.contributor.author Lastrucci, Claire
dc.contributor.author Duval, Carine
dc.contributor.author Mercier, Ingrid
dc.contributor.author Bénard, Alan
dc.contributor.author Capilla, Florence
dc.contributor.author Al Saati, Talal
dc.contributor.author Poincloux, Renaud
dc.contributor.author Kondova, Ivanela
dc.contributor.author Verreck, Frank A. W.
dc.contributor.author Cougoule, Céline
dc.contributor.author Maridonneau-Parini, Isabelle
dc.contributor.author Sasiain, Maria del Carmen
dc.contributor.author Neyrolles, Olivier
dc.date.accessioned 2019-11-18T08:33:00Z
dc.date.available 2019-11-18T08:33:00Z
dc.date.issued 2018
dc.description.abstract 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.
dc.format.mimetype application/pdf
dc.identifier.citation Lugo-Villarino G, Troegeler A, Balboa L, Lastrucci C, Duval C, Mercier I, Bénard A, Capilla F, Al Saati T, Poincloux R, Kondova I, Verreck FAW, Cougoule C, Maridonneau-Parini I, Sasiain MDC, Neyrolles O. The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis. Front Immunol. 2018; 9:1123. DOI 10.3389/fimmu.2018.01123
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2018.01123
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/42876
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Immunol. 2018; 9:1123
dc.rights © 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.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Macrophages
dc.subject.keyword Mycobacterium tuberculosis
dc.subject.keyword DC-SIGN
dc.subject.keyword C-type lectin receptors
dc.subject.keyword Anti-inflammatory
dc.title The C-Type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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