Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance

Nagatoshi Fujiwara, Steven A. Porcelli, Takashi Naka, Ikuya Yano, Shinji Maeda, Hirotaka Kuwata, Shizuo Akira, Satoshi Uematsu, Takemasa Takii, Hisashi Ogura, Kazuo Kobayashi

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1177-1184
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1831
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Ceramide
  • Sphingobacterium spiritivorum
  • Sphingophospholipid
  • Toll-like receptor (TLR) 4

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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