Triacylated lipoproteins derived from Mycoplasma pneumoniae activate nuclear factor-kappaB through toll-like receptors 1 and 2.
Pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributed to excessive immune responses. Recently, a mycoplasma lipoprotein has been shown to induce nuclear factor kappaB (NF-kappaB) activation through toll-like receptor 1 (TLR1), TLR2 and TLR6. In this study, we examined the ability of lipoproteins from M. pneumoniae to activate NF-kappaB through TLR1- and TLR2-dependent, but TLR6-independent, pathways, and the active components responsible for the NF-kappaB activation through the TLR6-independent pathway were identified. The active lipoproteins were found to be MPN611 and MPN162 of M. pneumoniae (designated N-ALP1 and N-ALP2, respectively). Purified N-ALP1 and N-ALP2 from M. pneumoniae and triacylated partial synthetic lipopeptides of N-ALP1 and N-ALP2 augmented the levels of NF-kappaB induction through TLR1- and TLR2-dependent pathways, whereas diacylated partial synthetic lipopeptides of N-ALP1 and N-ALP2 activated NF-kappaB through TLR1-, TLR2- and TLR6-dependent pathways. These data suggest that N-ALP1 and N-ALP2 would be triacylated lipoproteins. The activity of N-ALP1 and N-ALP2 was decreased with a pretreatment of lipoprotein lipase, and partially decreased by protease treatment, indicating that the lipid moiety of N-ALP1 and N-ALP2 is critical for the NF-kappaB activation. Thus, triacylated lipoproteins derived from M. pneumoniae might activate NF-kappaB through TLR1 and TLR2, but not TLR6.
Shimizu
Takashi
T
Department of Bacteriology, Kurume University School of Medicine, Kurume, Japan.
Kida
Yutaka
Y
Kuwano
Koichi
K
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D006358:Hot Temperature; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D051907:Lysosomal Membrane Proteins / Q000276:immunology; D008969:Molecular Sequence Data; D009177:Mycoplasma pneumoniae / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D051194:Toll-Like Receptor 1 / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000276:immunology
D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D008074:Lipoproteins; D051907:Lysosomal Membrane Proteins; D016328:NF-kappa B; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6