Lacticaseibacillus paracasei KW3110 induces interleukin-12 production via Toll-like receptor 8 in human macrophages and exerts immunomodulatory effects
Year: 2026
Type: article
Abstract: The global rise in allergic diseases necessitates safer and more effective therapeutic approaches. Lacticaseibacillus paracasei KW3110 (KW3110) exhibits potent interleukin-12 (IL-12)-inducing and anti-allergic effects. In this study, we investigated the underlying molecular mechanism of KW3110-induced IL-12 production using the macrophage-like differentiated THP-1 cell line and primary human macrophages differentiated from monocytes isolated from human peripheral blood mononuclear cells. Phagocytosis of KW3110 was demonstrated using pH-sensitive fluorescent labelling. A strong positive correlation between phagocytic uptake and IL-12 production was observed, and inhibition of phagocytosis abolished the induction of IL-12 production. Nucleic acids purified from KW3110 induced dose-dependent IL-12 production, and enzymatic digestion revealed that single-stranded RNA, but not double-stranded RNA or DNA, was essential for this induction. RNase A treatment of KW3110 itself abolished IL-12 production, and chloroquine inhibition of endosomal maturation suppressed the response. Using selective antagonists, we demonstrated that IL-12 production induced by KW3110 and its RNA was mediated primarily via endosomal Toll-like receptor 8 (TLR8). In a coculture of human naïve CD4+ T cells and monocyte-derived macrophages, macrophages stimulated with KW3110 induced interferon-gamma-producing T cells and suppressed T helper 2 (Th2)-associated cytokines. These results suggest that KW3110 promotes IL-12 production via TLR8 in human macrophages and enhances Th1 immunity.
Institutions: Kirin (Japan), Kirin Holdings Company, Limited (Japan)
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7213205866