Mycoplasma genitalium-derived lipid-associated membrane proteins activate NF-kappaB through toll-like receptors 1, 2, and 6 and CD14 in a MyD88-dependent pathway.
Mycoplasma genitalium is a leading pathogen of nongonoccocal chlamydia-negative urethritis, which has been implicated directly in numerous other genitourinary and extragenitourinary tract pathologies. The pathogenesis of infection is attributed in part to excessive immune responses. M. genitalium-derived lipid-associated membrane proteins (LAMPs) are a mixture of bacterial lipoproteins, exposed at the surface of mycoplasma, that are potent inducers of the host innate immune system. However, the interaction of M. genitalium-derived LAMPs as pathogenic agents with Toll-like receptors (TLRs) and the signaling pathways responsible for active inflammation and NF-kappaB activation have not been fully elucidated. In this study, LAMPs induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in a dose-dependent manner. Blocking assays showed that TLR2- and CD14-neutralizing antibodies reduced the expression of TNF-alpha and IL-6 in THP-1 cells. Furthermore, LAMP-induced NF-kappaB activation was increased in 293T cells transfected with TLR2 plasmid. The activity of NF-kappaB was synergically augmented by cotransfected TLR1, TLR6, and CD14. Additionally, LAMPs were shown to inhibit NF-kappaB expression by cotransfection with dominant-negative MyD88 and TLR2 plasmids. These results suggest that M. genitalium-derived LAMPs activate NF-kappaB via TLR1, TLR2, TLR6, and CD14 in a MyD88-dependent pathway.
Pathogenic Biology Institute, University of South China, Hengyang, China.
Jun
J
He
Xiaoxing
X
You
Yanhua
Y
Zeng
Minjun
M
Yu
Lingling
L
Zuo
Yimou
Y
Wu
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009175:Mycoplasma Infections / Q000276:immunology*; D045704:Mycoplasma genitalium / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007155:Immunologic Factors; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C434984:TIRAP protein, human; C495342:TLR2 protein, human; C495368:TLR6 protein, human