Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection

Frontiers in Immunology

Immunology

Ruslan Zvartsev¹  Juan Hidalgo²  Alexander Dyatlov³  Elena Kondratieva³  Anastasiya Tsareva³  Alexander Apt³  Irina Linge³ 

[1] Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia;Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain;Laboratory for Immunogenetics, Department of Immunology, Central Institute for Tuberculosis, Moscow, Russia;

关键词: tuberculosis;    B-cells;    IL-6;    lung inflammation;    T cells;   

DOI  :  10.3389/fimmu.2022.750068

 received in 2021-07-30, accepted in 2022-01-10,  发布年份 2022

来源: Frontiers

【 摘 要 】

The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background. Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4+IFN-γ+, Th17+, and CD4+CXCR5+ follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions.

【 授权许可】

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Copyright © 2022 Linge, Tsareva, Kondratieva, Dyatlov, Hidalgo, Zvartsev and Apt