B Cells Producing Type I Interferon Modulate Macrophage Polarization in Tuberculosis

HUDRISIER, DENIS; GICQUEL, BRIGITTE; ANTON-LEBERRE, VÉRONIQUE; NEYROLLES, OLIVIER; REHWINKEL, JAN; DEL CARMEN SASIAIN, MARIA; BOUDINOT, PIERRE; KAUFMANN, STEFAN HE; MERCIER, INGRID; LANG, ROLAND; SAKWA, IMME; JOUNEAU, LUC; COLOM, ANDRÉ; BÉNARD, ALAN; FILLATREAU, SIMON; O'GARRA, ANNE; LOXTON, ANDRE G; AL-SAATI, TALAL; TAILLEUX, LUDOVIC; SCHIERLOH, PABLO

AMERICAN JORUNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

American Thoraxic Society

Año: 2017

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, 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.