B cells inhibit IL-1 family cytokine production and Mycobacterium tuberculosis growth in human CD14+ cells 9263

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Abstract Description The IL-1 superfamily of cytokines (ILSF) produced by antigen-presenting cells plays important roles in Mycobacterium tuberculosis (Mtb) infection. In present study, we infected human monocyte-derived macrophages (MDMs) with Mtb and measured ILSF production, determined effects of ILSF on Mtb growth via use of recombinant cytokines and antibodies, and determined expression of death pathway genes involved in ILSF mediated Mtb growth. We determined the effects of B and NK cells on ILSF production by human monocytes. Further we determined the effect of B cells on Mtb growth in human monocytes. Mtb infection significantly increased production of IL-1α, IL-1β, IL-18, and IL-37 and reduced production of IL-1Ra by MDMs. Human rIL-1α, rIL-1β, rIL-18, and rIL-33 reduced Mtb growth in MDMs. In contrast, human rIL-1Ra enhanced Mtb growth in MDMs. Neutralizing antibodies to IL-1α, IL-1β and IL-18 enhanced Mtb growth, and neutralizing antibodies to IL-1Ra and IL-33 reduced Mtb growth in MDMs. Mtb infection increased expression of Cas3, LC3B expression by MDMs and rIL-1b and rIL-36 further increased Cas3 expression, and rIL-1α and rIL-33 reduced LC3B expression. B cells significantly reduced IL-1α, IL-1β, IL-6 and TNF-α production, enhanced IL-1Ra, IL-18 and IL-10 production, and inhibited Mtb growth in human CD14+ monocytes. The finds are related to TB granulomas where B cells may regulate balance of pro- and anti- inflammatory ILSF and inhibit TB growth. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

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