Recombinant human interleukin-32γ facilitates macrophage phagocytosis of Streptococcus pneumoniae by activating nuclear factor kappa B-soluble epoxide hydrolase pathway.

Interleukin-32 is recognized as a potent proinflammatory mediator in various infectious contexts; however, its precise contribution to host defense against Streptococcus pneumoniae (S.pn) remains to be fully elucidated. This study demonstrates that S.pn challenge robustly upregulates interleukin-32 expression in human peripheral blood mononuclear cells and THP-1 cells. Functional assays reveal that exogenous recombinant human interleukin-32γ significantly potentiates the phagocytic activity of both murine (RAW 264.7) and human (THP-1-derived) macrophages against S.pn. Mechanistically, recombinant human interleukin-32γ-induced phagocytosis is mediated by the upregulation and secretion of soluble epoxide hydrolase (sEH), a process contingent upon the activation of the nuclear factor κB (NF-κB) signaling pathway. Furthermore, pharmacological inhibition of either NF-κB or sEH effectively abrogates the prophagocytic effects of recombinant human interleukin-32γ, confirming the functional requirement of the NF-κB-sEH axis in this response. Collectively, these results elucidate a novel interleukin-32γ-NF-κB-sEH regulatory cascade that facilitates macrophage-mediated bacterial clearance, thereby identifying a potential therapeutic target for the management of pneumococcal infections.