Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection
Linge, Irina (Central Institute for Tuberculosis (Rússia))
Tsareva, Anastasiya (Central Institute for Tuberculosis (Rússia))
Kondratieva, Elena (Central Institute for Tuberculosis (Rússia))
Dyatlov, Alexander (Central Institute for Tuberculosis (Rússia))
Hidalgo Pareja, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Zvartsev, Ruslan (Russian Academy of Sciences)
Apt, Alexander (Central Institute for Tuberculosis (Rússia))

Fecha:	2022
Resumen:	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.
Ayudas:	Ministerio de Economía, Industria y Competitividad RTI2018-101105-B-100
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Tuberculosis ; B-cells ; IL-6 ; Lung inflammation ; T cells
Publicado en:	Frontiers in immunology, Vol. 13 (january 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.750068
PMID: 35154093

11 p, 4.9 MB

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