• Alan Bénard, Imme Sakwa, Pablo Schierloh, André Colom, Ingrid Mercier, Ludovic Tailleux, Luc Jouneau, Pierre Boudinot, Talal Al-Saati, Roland Lang, Jan Rehwinkel, Andre G Loxton, Kaufmann Stefan H E SHE 14 Department of Immunology, Max Planck Institute of Infection Biology, Berlin, Germany., Véronique Anton-Leberre, Anne O'Garra, Sasiain Maria Del Carmen MDC 2 International Associated Laboratory CNRS "IM-TB/HIV (Immunometabolism and Macrophages in Tuberculosis/Human Immunodeficiency Virus-1 Co-inf, Brigitte Gicquel, Simon Fillatreau, Olivier Neyrolles, and Denis Hudrisier.
• 1 Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier, Toulouse, France.
• Am. J. Respir. Crit. Care Med. 2018 Mar 15; 197 (6): 801-813.

RationaleIn 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.ObjectivesTo document the role of B cells in TB in an unbiased manner.MethodsWe 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 ResultsB 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.ConclusionsType I IFN produced by Mtb-stimulated B cells favors macrophage polarization toward a regulatory/antiinflammatory phenotype during Mtb infection.

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