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Am J Respir Crit Care Med. 2018 Mar 15;197(6):801-813. doi: 10.1164/rccm.201707-1475OC.

B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis.

Author information

1
1 Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier, Toulouse, France.
2
2 International Associated Laboratory CNRS "IM-TB/HIV (Immunometabolism and Macrophages in Tuberculosis/Human Immunodeficiency Virus-1 Co-infection)," Toulouse, France, and Buenos Aires, Argentina.
3
3 Department of Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany.
4
4 Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Berlin, Germany.
5
5 Instituto de Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, Academia Nacional de Medicina, Pacheco de Melo, Buenos Aires, Argentina.
6
6 Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Université de Toulouse, CNRS, Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées, Toulouse, France.
7
7 Unit of Mycobacterial Genetics and.
8
8 Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, Paris, France.
9
9 Virologie et Immunologie Moléculaires, INRA, Jouy-en-Josas, France.
10
10 Institut National de la Santé et de la Recherche Médicale (INSERM)/Université Paul Sabatier/École Nationale Vétérinaire de Toulouse/Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales, Service d'Histopathologie, Centre Hospitalier Universitaire, Purpan, Toulouse, France.
11
11 Institute of Clinical Microbiology, Immunology, and Hygiene, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
12
12 Radcliffe Department of Medicine, Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
13
13 South African Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
14
14 Department of Immunology, Max Planck Institute of Infection Biology, Berlin, Germany.
15
15 Division of Immunoregulation, Medical Research Council, National Institute for Medical Research, London, United Kingdom.
16
16 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
17
17 Institut Necker-Enfants Malades, INSERM U1151-CNRS Unité Mixte de Recherche 8253, Paris, France.
18
18 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and.
19
19 Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France.

Abstract

RATIONALE:

In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or noninfectious diseases via antibody-independent mechanisms. In tuberculosis (TB), B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understood.

OBJECTIVES:

To document the role of B cells in TB in an unbiased manner.

METHODS:

We generated the transcriptome of B cells isolated from Mycobacterium tuberculosis (Mtb)-infected mice and validated the identified key pathways using in vitro and in vivo assays. The obtained data were substantiated using B cells from pleural effusion of patients with TB.

MEASUREMENTS AND MAIN RESULTS:

B cells isolated from Mtb-infected mice displayed a STAT1 (signal transducer and activator of transcription 1)-centered signature, suggesting a role for IFNs in B-cell response to infection. B cells stimulated in vitro with Mtb produced type I IFN, via a mechanism involving the innate sensor STING (stimulator of interferon genes), and antagonized by MyD88 (myeloid differentiation primary response 88) signaling. In vivo, B cells expressed type I IFN in the lungs of Mtb-infected mice and, of clinical relevance, in pleural fluid from patients with TB. Type I IFN expression by B cells induced an altered polarization of macrophages toward a regulatory/antiinflammatory profile in vitro. In vivo, increased provision of type I IFN by B cells in a murine model of B cell-restricted Myd88 deficiency correlated with an enhanced accumulation of regulatory/antiinflammatory macrophages in Mtb-infected lungs.

CONCLUSIONS:

Type I IFN produced by Mtb-stimulated B cells favors macrophage polarization toward a regulatory/antiinflammatory phenotype during Mtb infection.

KEYWORDS:

B lymphocytes; IFN; macrophages; tuberculosis

PMID:
29161093
PMCID:
PMC5855072
DOI:
10.1164/rccm.201707-1475OC
[Indexed for MEDLINE]
Free PMC Article

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