Intraperitoneal immunization with oligomannose-coated liposome-entrapped soluble leishmanial antigen induces antigen-specific T-helper type immune response in BALB/c mice through uptake by peritoneal macrophages.
The present study demonstrates that the intraperitoneal administration of soluble leishmanial antigen (SLA) entrapped in liposomes coated with neoglycolipids containing oligomannose residues (mannopentaose or mannotriose) strongly induces an antigen-specific T-helper type 1 (Th1) immune response in BALB/c mice. In response to in vitro stimulation with SLA, spleen cells from mice that had received oligomannose-coated liposomes encasing SLA (SLA-OML) displayed greater interferon (IFN)-gamma and interleukin (IL)-2 production and lower IL-4 and IL-5 production than spleen cells from mice that had received SLA alone, indicating that the SLA-specific Th1 immune response had predominantly been induced in the mice that had received SLA-OML. After subsequent infection with Leishmania major, mice that had received SLA-OML were effectively protected against the disease, with a predominant production of IFN-gamma. OML were preferentially and rapidly incorporated into peritoneal macrophages, and the transplantation of macrophages containing SLA-OML into the peritoneal cavity also induced protection against L. major infection. Thus, SLA-OML were shown to successfully induce a specific Th1 immune response capable of controlling L. major infection in BALB/c mice through the effective uptake of OML by peritoneal macrophages.
Shimizu
Y
Y
Institute of Glycotechnology, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
Takagi
H
H
Nakayama
T
T
Yamakami
K
K
Tadakuma
T
T
Yokoyama
N
N
Kojima
N
N
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007114:Immunization; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008358:Mannose / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000008:administration & dosage*; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000953:Antigens, Protozoan; D039481:CD11b Antigen; D016207:Cytokines; D008081:Liposomes; D009844:Oligosaccharides; D016052:Protozoan Vaccines; D008358:Mannose