Lacticaseibacillus paracasei KW3110 induces interleukin-12 production via Toll-like receptor 8 in human macrophages and exerts immunomodulatory effects
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.
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BibTeX
@article{ochiai2026lacticaseibacillus,
title = {{Lacticaseibacillus paracasei KW3110 induces interleukin-12 production via Toll-like receptor 8 in human macrophages and exerts immunomodulatory effects}},
author = {Keita OCHIAI and Kana WATANABE and Shinya NANAUMI and Masaya KANAYAMA},
journal = {Bioscience of Microbiota, Food and Health},
year = {2026},
month = sep,
doi = {10.12938/bmfh.2025-075},
url = {https://www.jstage.jst.go.jp/article/bmfh/advpub/0/advpub_2025-075/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Lacticaseibacillus paracasei KW3110 induces interleukin-12 production via Toll-like receptor 8 in human macrophages and exerts immunomodulatory effects
AU - Keita OCHIAI
AU - Kana WATANABE
AU - Shinya NANAUMI
AU - Masaya KANAYAMA
PY - 2026
DA - 2026/09/15
JO - Bioscience of Microbiota, Food and Health
DO - 10.12938/bmfh.2025-075
UR - https://www.jstage.jst.go.jp/article/bmfh/advpub/0/advpub_2025-075/_article
AB - 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.
SN - 2186-3342
ER -