TY - JOUR
T1 - Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway
AU - Inoue, Joe
AU - Ideue, Ryuichi
AU - Takahashi, Daisuke
AU - Kubota, Masahiro
AU - Kumazawa, Yoshio
N1 - Funding Information:
We are grateful to Mr. S. Amimori and Ms. S. Watanabe for their technical assistance. We are grateful to Ms. N. Nemoto for performing the electron microscopy. This work was supported in part by a grant-in-aid from Kitasato University Research Grant for Young Researchers to JI.
PY - 2009/1/5
Y1 - 2009/1/5
N2 - Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-γ from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes. GSL-liposomes containing DOPE were clearly broken in late endosomes and this may facilitate effective loading of GSLs onto CD1 molecules. Treatment with GSL-liposomes also activated NKT cells and DCs in vivo. Collectively, our results strongly suggest that GSL-liposomes can effectively induce NKT cell-mediated immune responses and may be useful as an immune adjuvant for inducing protective immunity.
AB - Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-γ from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes. GSL-liposomes containing DOPE were clearly broken in late endosomes and this may facilitate effective loading of GSLs onto CD1 molecules. Treatment with GSL-liposomes also activated NKT cells and DCs in vivo. Collectively, our results strongly suggest that GSL-liposomes can effectively induce NKT cell-mediated immune responses and may be useful as an immune adjuvant for inducing protective immunity.
KW - Endosome
KW - Glycosphingolipid
KW - IFN-γ
KW - Liposome
KW - Natural killer T cell
UR - http://www.scopus.com/inward/record.url?scp=57049146298&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57049146298&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2008.09.078
DO - 10.1016/j.jconrel.2008.09.078
M3 - Article
C2 - 18930085
AN - SCOPUS:57049146298
SN - 0168-3659
VL - 133
SP - 18
EP - 23
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -