B cells inhibit IL-1 family cytokine production and <i>Mycobacterium tuberculosis</i> growth in human CD14+ cells

The IL-1 family of cytokines produced by antigen-presenting cells plays important roles in various diseases and infections, including Mycobacterium tuberculosis (Mtb) infection. In the present study, we infected human monocyte-derived macrophages (MDMs) with Mtb. Then, we measured the production of IL-1 superfamily (ILSF) cytokines (8 soluble factors) and determined the effects of ILSF cytokines on Mtb growth via the use of recombinant cytokines and antibodies. Mtb infection significantly increased the production of IL-1α, IL-1β, IL-18, and IL-37 and reduced the production of IL-1Ra by MDMs. Human recombinant IL-1α, IL-1β, and IL-18 reduced Mtb growth in MDMs. In contrast, human recombinant IL-1Ra enhanced Mtb growth in MDMs. Neutralizing antibodies against IL-1α, IL-1β, and IL-18 enhanced Mtb growth, and neutralizing antibodies against IL-1Ra and IL-33R reduced Mtb growth in MDMs. B cells are known to regulate inflammation in tuberculosis (TB) granulomas. We also determined the effects of B and NK cells on ILSF cytokine production by human monocytes. Furthermore, we determined the effect of B cells on Mtb growth in human monocytes. 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. These findings may be relevant in human TB granulomas, where B cells may regulate the balance of proinflammatory and anti-inflammatory ILSF cytokines and inhibit TB growth.