Human IL-6-Producing B Cells Promote the Differentiation of Monocytes Toward an Anti-Inflammatory CD16⁺CD163⁺CD206⁺PD-L1⁺ Phenotype in Tuberculosis
Corresponding Author
Alan Bénard
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Department of Surgery, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
Search for more papers by this authorLuciana Balboa
Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorMaxime Caouaille
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorLea Ravon-Katossky
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorEtienne Meunier
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorSimon Fillatreau
Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
Université Paris Cité, Faculté de Médecine, Paris, France
AP-HP, Hôpital Necker-Enfants Malades, Paris, France
Search for more papers by this authorMaria Del Carmen Sasiain
Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorOlivier Neyrolles
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorCorresponding Author
Denis Hudrisier
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorCorresponding Author
Alan Bénard
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Department of Surgery, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
Search for more papers by this authorLuciana Balboa
Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorMaxime Caouaille
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorLea Ravon-Katossky
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorEtienne Meunier
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorSimon Fillatreau
Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMR 8253, Université de Paris, Paris, France
Université Paris Cité, Faculté de Médecine, Paris, France
AP-HP, Hôpital Necker-Enfants Malades, Paris, France
Search for more papers by this authorMaria Del Carmen Sasiain
Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorOlivier Neyrolles
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
International Associated Laboratory (LIA) CNRS IM-TB/HIV (1167) / International Research Project Toulouse, France, Buenos Aires, Argentina
Search for more papers by this authorCorresponding Author
Denis Hudrisier
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
Search for more papers by this authorFunding: This research was supported by the Argentinean National Agency of Promotion of Science and Technology, Agence Nationale de la Recherche BTB-12-BSV3-0002, Fondation Bettencourt Schueller Explore-TB and Coup d'Elan, Deutsche Forschungsgemeinschaft BE6981/1-1, BE6981/4-1.
ABSTRACT
The polarization of the monocyte/macrophage compartment toward an anti-inflammatory profile is considered detrimental in tuberculosis (TB), but the factors controlling M2 polarization in this context are still poorly understood. Here, we found that B cells promote the differentiation of human monocytes toward an M2-like activation program through a process primarily dependent on IL-6 and the activation of STAT3 signaling in monocytes. This confers monocytes with immunomodulatory properties characterized by a reduced ability to produce proinflammatory cytokines and to stimulate IFNγ secretion by allogeneic T cells. Our findings were validated using B cells from TB patients, which constitutively produce high levels of IL-6, underscoring the clinical relevance of our experimental observations. Collectively, our results indicate that human B-cell-derived IL-6 might impair TB immunity by driving monocyte polarization toward an anti-inflammatory phenotype.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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