Liang_2026_J.Leukoc.Biol__

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