Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2: role of N-terminal hydrophobic portion in its multiple functions.

摘要: M161Ag is a 43-kDa surface lipoprotein of Mycoplasma fermentans, serving as potent cytokine inducer for monocytes/macrophages, maturing dendritic cells (DCs), and activating host complement on affected cells. It possesses unique N-terminal lipo-amino acid, S:-diacylglyceryl cysteine. The 2-kDa macrophage-activating lipopeptide-2 (MALP-2), recently identified ligand Toll-like receptor 2 (TLR2), derived from M161Ag. In this study, we structural motifs sustaining the functions using wild-type unlipidated rM161Ag with (SP(+)) or without signal peptides (SP(-)). Because SP(+) formed dimers via 25Cys, obtained monomeric form by mutagenesis (SP(+)C25S). Only wild type accelerated maturation human DCs determined CD83/86 criteria, suggesting importance fatty acids function. Wild-type monomer induced secretion TNF-alpha IL-12 p40 monocytes DCs. Either lipid peptide at portion was required expression contrast, murine macrophages produced in response to type, but not any recombinant M161Ag, species-dependent rM161Ag. both dimeric forms possessed ability activate alternative pathway. Again, hydrophobic associated These results, together finding that TLR2-deficient mice did produce infer structure important TLR2-mediated cell activation activation.