2001年2月15日
Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by toll-like receptor 2: Role of N-terminal hydrophobic portion in its multiple functions
Journal of Immunology
- 巻
- 166
- 号
- 4
- 開始ページ
- 2610
- 終了ページ
- 2616
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.4049/jimmunol.166.4.2610
M161Ag is a 43-kDa surface lipoprotein of Mycoplasma fermentans, serving as a potent cytokine inducer for monocytes/macrophages, maturing dendritic cells (DCs), and activating host complement on affected cells. It possesses a unique N-terminal lipoamino acid, S-diacylglyceryl cysteine. The 2-kDa macrophage-activating lipopeptide-2 (MALP-2), recently identified as a ligand for Toll-like receptor 2 (TLR2), is derived from M161Ag. In this study, we identified structural motifs sustaining the functions of M161Ag using wild-type and unlipidated rM161Ag with (SP+) or without signal peptides (SP-). Because the SP+ rM161Ag formed dimers via 25Cys, we obtained a monomeric form by mutagenesis (SP+C25S). Only wild type accelerated maturation of human DCs as determined by the CD83/86 criteria, suggesting the importance of the N-terminal fatty acids for this function. Wild-type and the SP+ form of monomer induced secretion of TNF-α and IL-12 p40 by human monocytes and DCs. Either lipid or signal peptide at the N-terminal portion of monomer was required for expression of this function. In contrast, murine macrophages produced TNF-α in response to wild type, but not to any recombinant form of M161Ag, suggesting the species-dependent response to rM161Ag. Wild-type and both monomeric and dimeric SP+ forms possessed the ability to activate complement via the alternative pathway. Again, the hydrophobic portion was associated with this function. These results, together with the finding that macrophages from TLR2-deficient mice did not produce TNF-α in response to M161Ag, infer that the N-terminal hydrophobic structure of M161Ag is important for TLR2-mediated cell activation and complement activation.
- リンク情報
-
- DOI
- https://doi.org/10.4049/jimmunol.166.4.2610
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/11160323
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0035865058&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=0035865058&origin=inward
- ID情報
-
- DOI : 10.4049/jimmunol.166.4.2610
- ISSN : 0022-1767
- PubMed ID : 11160323
- SCOPUS ID : 0035865058