TY - JOUR
T1 - Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance
AU - Fujiwara, Nagatoshi
AU - Porcelli, Steven A.
AU - Naka, Takashi
AU - Yano, Ikuya
AU - Maeda, Shinji
AU - Kuwata, Hirotaka
AU - Akira, Shizuo
AU - Uematsu, Satoshi
AU - Takii, Takemasa
AU - Ogura, Hisashi
AU - Kobayashi, Kazuo
N1 - Funding Information:
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan , and the Japan Health Sciences Foundation (to N.F.).
PY - 2013/6
Y1 - 2013/6
N2 - Sphingobacterium spiritivorum has five unusual sphingophospholipids (SPLs). Our previous study determined the complete chemical structures of these SPLs. The compositions of the long-chain bases/fatty acids in the ceramide portion, isoheptadecasphingosine/isopentadecanoate or isoheptadecasphingosine/2-hydroxy isopentadecanoate, are characteristic. The immune response against bacterial lipid components is considered to play important roles in microbial infections. It is reported that several bacterial sphingolipids composed of ceramide are recognized by CD1-restricted T and NKT cells and that a non-peptide antigen is recognized by γδ T cells. In this study, we demonstrated that these bacterial SPLs activated murine bone marrow macrophages (BMMs) via Toll-like receptor (TLR) 4 but not TLR2, although they slightly activated CD1d-restricted NKT and γδT cells. Interestingly, this TLR 4-recognition pathway of bacterial SPLs involves the fatty acid composition of ceramide in addition to the sugar moiety. A non-hydroxy fatty acid composed of ceramide was necessary to activate murine BMMs. The bacterial survival was significantly higher in TLR4-KO mice than in TLR2-KO and wild-type mice. The results indicate that activation of the TLR4-dependent pathway of BMMs by SPLs induced an innate immune response and contributed to bacterial clearance.
AB - Sphingobacterium spiritivorum has five unusual sphingophospholipids (SPLs). Our previous study determined the complete chemical structures of these SPLs. The compositions of the long-chain bases/fatty acids in the ceramide portion, isoheptadecasphingosine/isopentadecanoate or isoheptadecasphingosine/2-hydroxy isopentadecanoate, are characteristic. The immune response against bacterial lipid components is considered to play important roles in microbial infections. It is reported that several bacterial sphingolipids composed of ceramide are recognized by CD1-restricted T and NKT cells and that a non-peptide antigen is recognized by γδ T cells. In this study, we demonstrated that these bacterial SPLs activated murine bone marrow macrophages (BMMs) via Toll-like receptor (TLR) 4 but not TLR2, although they slightly activated CD1d-restricted NKT and γδT cells. Interestingly, this TLR 4-recognition pathway of bacterial SPLs involves the fatty acid composition of ceramide in addition to the sugar moiety. A non-hydroxy fatty acid composed of ceramide was necessary to activate murine BMMs. The bacterial survival was significantly higher in TLR4-KO mice than in TLR2-KO and wild-type mice. The results indicate that activation of the TLR4-dependent pathway of BMMs by SPLs induced an innate immune response and contributed to bacterial clearance.
KW - Ceramide
KW - Sphingobacterium spiritivorum
KW - Sphingophospholipid
KW - Toll-like receptor (TLR) 4
UR - http://www.scopus.com/inward/record.url?scp=84876897609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876897609&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2013.03.008
DO - 10.1016/j.bbalip.2013.03.008
M3 - Article
C2 - 23545566
AN - SCOPUS:84876897609
SN - 1388-1981
VL - 1831
SP - 1177
EP - 1184
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 6
ER -