Mycobacterium tuberculosis Mannose-Capped Lipoarabinomannan Induces IL-10-Producing B Cells and Hinders CD4+Th1 Immunity

• Main Authors: Chunhui Yuan, Zi-Lu Qu, Xiao-Lei Tang, Qi Liu, Wei Luo, Chun Huang, Qin Pan, Xiao-Lian Zhang
• Format: Article
• Language: English
• Published: Elsevier 2019-01-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004218302293

Summary: The importance of Th1/interferon (IFN)-γ-mediated responses in mycobacterial infection has been well established. However, little is known about B cell-mediated immunity during Mycobacterium tuberculosis (Mtb) infection. Interleukin (IL)-10-producing B cells (B10 cells), a subset of B regulatory cells (Bregs), are implicated in modulating the immune response. Herein, we found that B10 cells were significantly increased in patients with tuberculosis. Furthermore, mannose-capped lipoarabinomannan (ManLAM), a major surface lipoglycan component from Mtb, induced a significant increase in B10 cells, which enriched in CD5+ B1a B cells. ManLAM induced IL-10 production mainly by activating MyD88/PI3K/AKT/Ap-1 and K63-linked ubiquitination of NF-κB essential modulator/nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathways in B cells via Toll-like receptor 2. IL-10 production by ManLAM-treated B cells further inhibited CD4+ Th1 polarization, leading to increased susceptibility to mycobacterial infection compared with ManLAM-treated IL-10−/− B group. Thus, we report a new immunoregulation mechanism in which Mtb ManLAM-induced B10 cells negatively regulate host anti-TB cellular immunity. : Bacterium; Biological Sciences; Immune Response; Microbiology Subject Areas: Bacterium, Biological Sciences, Immune Response, Microbiology