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

Chunhui Yuan; Zi-Lu Qu; Xiao-Lei Tang; Qi Liu; Wei Luo; Chun Huang; Qin Pan; Xiao-Lian Zhang

doi:10.1016/j.isci.2018.11.039

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

iScience. 2019 Jan 25:11:13-30. doi: 10.1016/j.isci.2018.11.039. Epub 2018 Dec 4.

Authors

Chunhui Yuan¹, Zi-Lu Qu², Xiao-Lei Tang², Qi Liu², Wei Luo², Chun Huang², Qin Pan³, Xiao-Lian Zhang⁴

Affiliations

¹ State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuchang, Wuhan 430071, China; Department of Laboratory Medicine, Wuhan Children's Hospital, Huazhong University of Science and Technology, Jiangan, Wuhan 430015, China.
² State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuchang, Wuhan 430071, China.
³ State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuchang, Wuhan 430071, China. Electronic address: panqincn@whu.edu.cn.
⁴ State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuchang, Wuhan 430071, China. Electronic address: zhangxiaolian@whu.edu.cn.

Abstract

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.

Keywords: Bacterium; Biological Sciences; Immune Response; Microbiology.