title: Intracellular delivery of lipopolysaccharide induces effective Th1-immune responses independent of IL-12.
abstract: Lipopolysaccharide (LPS) is responsible for many of the inflammatory responses and pathogenic effects of Gram-negative bacteria, however, it also induces protective immune responses. LPS induces the production of inflammatory cytokines such as TNF-α, IL-6, and IL-12 from dendritic cells (DCs) and macrophages. It is thought that IL-12 is required for one of the protective immune responses induced by LPS, the T helper 1 (Th1)-immune response, which include the production of IFN-γ from Th1cells and IgG2c class switching. Here, we clearly demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS-liposomes) does not induce the production of inflammatory cytokines from DCs, but enhances Th1-immune responses via type-I IFNs, independent of IL-12. Collectively, our results strongly suggest that LPS-liposomes can effectively induce Th1-immune responses without inducing unnecessary inflammation, and may be useful as an immune adjuvant to induce protective immunity.
authors.affiliation: Department of Biosciences, School of Science and Graduate School of Science, Kitasato University, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Joe
authors.initials: J
authors.lastname: Inoue
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D008081:Liposomes; D016328:NF-kappa B; D018664:Interleukin-12; D016899:Interferon-beta