title: Requirement of TLR4 signaling for the induction of a Th1 immune response elicited by oligomannose-coated liposomes.
abstract: We have previously demonstrated that administration of oligomannose-coated liposomes (OMLs), in which an antigen is encased, induce antigen-specific Th1 immune responses and CTLs. In the present study, we showed that TLR4 signaling is required for the induction of specific immune responses following OML administration. In C3H/HeJ mice, which express a dysfunctional TLR4, the antigen-specific Th1 immune response could not be elicited following intraperitoneal administration of OVA-encased OMLs (OML/OVA). However, OML uptake by peritoneal cells, the subsequent production of IL-12 and the upregulation of co-stimulatory molecules and MHC class II on the cells in response to OML uptake occurred in C3H/HeJ mice to the same extent as in wild type C3H/HeN mice. In addition, peritoneal phagocytic cells from TLR4(-/-) mice that ingest OML/OVA can activate CD4(+) T cells from OT-II mice. On the other hand, the number of OML-ingesting peritoneal cells that migrated into mesenteric lymph nodes in C3H/HeJ mice was significantly less than that in C3H/HeN mice. Therefore, the chemotactic capability of OML-ingesting peritoneal phagocytes to the draining lymph nodes rather than the activation and maturation of the cells in response to OML uptake is impaired by lack of TLR4 signaling, and disorder of the Th1 immune response elicited by OMLs in mice, which lack TLR4 signaling, is due to the impairment of cell migration following OML uptake.
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Yamatani
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan. Electronic address: naoyaki@keyaki.cc.u-tokai.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007109:Immunity; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008081:Liposomes; D009844:Oligosaccharides; D051197:Toll-Like Receptor 4; C028569:oligomannoside
keywords: Cell migration; Oligomannose-coated liposomes; TLR; Th1 immune response