B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis

SAKWA I; MERCIER I; BOUDINOT P; REHWINKEL J; ANTON-LEBERRE V; GICQUEL B; HUDRISIER D; BÉNARD A; SCHIERLOH P; ANDRE COLOM; TAILLEUX L; JOUNEAU L; AL-SAATI T; LANG R; LOXTON AG; KAUFMANN SHE; O'GARRA A; SASIAIN MDC; FILLATREAU S; NEYROLLES O

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

AMER THORACIC SOC

Lugar: New York; Año: 2018

1073-449X

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 (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 patientswith TB.Measurements and Main Results: B cells isolated from Mtb-infected mice displayed a STAT1 (signal transducerand activator of transcription 1)-centered signature, suggestinga role for IFNs in B-cell response to infection. B cells stimulatedin vitro with Mtb produced type I IFN, via a mechanisminvolving the innate sensor STING (stimulator of interferongenes), and antagonized by MyD88 (myeloid differentiationprimary response 88) signaling. In vivo, B cells expressed type IIFN in the lungs of Mtb-infected mice and, of clinical relevance,in pleural fluid from patients with tuberculosis. Type I IFNexpression by B cells induced an altered polarization ofmacrophages toward a regulatory/antiinflammatory profilein vitro. In vivo, increased provision of type I IFN by B cells ina 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.