B Cells Producing Type I Interferon Modulate Macrophage Polarization in Tuberculosis

Benard A, Sakwa I, Schierloh P, Colom A, Mercier I, Tailleux L, Jouneau L, Boudinot P, Al-Saati T, Lang R, Rehwinkel J, Loxton AG, Kaufmann SHE, Anton-Leberre V, O'Garra A, Del Carmen Sasiain M, Gicquel B, Fillatreau S, Neyrolles O, Hudrisier D (2017)

Publication Type: Journal article

Publication year: 2017

Journal

American Journal of Respiratory and Critical Care Medicine American Thoracic Society

DOI: 10.1164/rccm.201707-1475OC

Abstract

RATIONALE: In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or non-infectious diseases via antibody-independent mechanisms. In tuberculosis, 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 tuberculosis 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 tuberculosis patients. MEASUREMENTS AND MAIN RESULTS: B cells isolated from Mtb-infected mice displayed a STAT1-centered signature, suggesting a role for interferons in B cell response to infection. B cells stimulated in vitro with Mtb produced type I interferon, via a mechanism involving the innate sensor STING, and antagonized by MyD88 signaling. In vivo, B cells expressed type I interferon in the lungs of Mtb-infected mice and, of clinical relevance, in pleural fluid from patients with tuberculosis. Type I interferon expression by B cells induced an altered polarization of macrophages towards a regulatory/anti-inflammatory profile in vitro. In vivo, increased provision of type I interferon by B cells in a murine model of B cell-restricted Myd88-deficiency correlated with an enhanced accumulation of regulatory/anti-inflammatory macrophages in Mtb infected lungs. CONCLUSION: Type I interferon produced by Mtb-stimulated B cells favors macrophage polarization towards a regulatory/anti-inflammatory phenotype during Mtb infection.

Involved external institutions

Université Toulouse III - Paul Sabatier FR France (FR) French National Institute for Agricultural Research / Institut Nationale de la Recherche Agronomique (INRA) FR France (FR) University of Stellenbosch / Universiteit van Stellenbosch ZA South Africa (ZA) Deutsches Rheuma-Forschungszentrum (DRFZ) DE Germany (DE) Max-Planck-Institut für Infektionsbiologie / Max Planck Institute for Infection Biology DE Germany (DE) Université Fédérale de Toulouse Midi-Pyrénées FR France (FR) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) FR France (FR) University of Oxford GB United Kingdom (GB) National Institute for Medical Research GB United Kingdom (GB) Institut Pasteur FR France (FR)

How to cite

APA:

Benard, A., Sakwa, I., Schierloh, P., Colom, A., Mercier, I., Tailleux, L.,... Hudrisier, D. (2017). B Cells Producing Type I Interferon Modulate Macrophage Polarization in Tuberculosis. American Journal of Respiratory and Critical Care Medicine. https://dx.doi.org/10.1164/rccm.201707-1475OC

MLA:

Benard, Alan, et al. "B Cells Producing Type I Interferon Modulate Macrophage Polarization in Tuberculosis." American Journal of Respiratory and Critical Care Medicine (2017).

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