B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis

Area of Science:

• Immunology
• Infectious Diseases

Background:

• B lymphocytes contribute to disease pathogenesis through antibody-independent mechanisms.
• The precise role of B cells in tuberculosis (TB) remains unclear despite their accumulation in the lungs.

Purpose of the Study:

• To comprehensively investigate the function of B cells in TB pathogenesis.
• To elucidate the antibody-independent mechanisms employed by B cells during M. tuberculosis infection.

Main Methods:

• Transcriptome analysis of B cells from M. tuberculosis-infected mice.
• In vitro and in vivo validation of identified pathways.
• Analysis of B cells from TB patients' pleural effusions.

Main Results:

• B cells from infected mice exhibited a STAT1-centered gene expression profile, indicating a role for interferons (IFNs).
• M. tuberculosis-stimulated B cells produced type I IFN via STING signaling, antagonized by MyD88.
• Type I IFN-producing B cells were found in the lungs of infected mice and pleural fluid of TB patients.
• B cell-derived type I IFN promoted a regulatory/anti-inflammatory macrophage phenotype in vitro and in vivo.

Conclusions:

• Type I IFN produced by M. tuberculosis-stimulated B cells drives macrophage polarization towards a regulatory/anti-inflammatory phenotype.
• This mechanism suggests a significant role for B cells in modulating the host immune response during TB.