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

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 cel...

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Detalles Bibliográficos
Autores principales: Yuan, Chunhui, Qu, Zi-Lu, Tang, Xiao-Lei, Liu, Qi, Luo, Wei, Huang, Chun, Pan, Qin, Zhang, Xiao-Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299163/
https://www.ncbi.nlm.nih.gov/pubmed/30572206
http://dx.doi.org/10.1016/j.isci.2018.11.039
Descripción
Sumario: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.