CVI Accepts, published online ahead of print on 30 September 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00281-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mycoplasma genitalium-derived lipid-associated membrane proteins activate NF-B through TLR2/TLR1/TLR6 and CD14 in MyD88-dependent pathway

Jun He, Xiaoxing You, Yanhua Zeng, Minjun Yu, Lingling Zuo, and Yimou Wu^*

Pathogenic Biology Institute, University of South China, Hengyang, China, 421001

^* To whom correspondence should be addressed. Email: yimouwu{at}sina.com.

Mycoplasma genitalium is a leading pathogen of nongonoccocal chlamydia-negative urethritis which has been directly implicated in other numerous genitourinary and extragenitourinary tract pathologies. The pathogenesis of infection is in part attributed to excessive immune responses. M. genitalium-derived lipid-associated membrane proteins (LAMPs) are the mixture of bacterial lipoprotein, exposed at the surface of mycoplasma, which are potent inducers of the host innate immune system. However, the interaction of M. genitalium-derived LAMPs as pathogenic agents with TLRs and signaling pathway are responsible for active inflammation and NF-B activation have not been fully elucidated. In this study, LAMPs induced the production of TNF- and IL-6 in a dose-dependent manner. Blocking assays showed that TLR2 and CD14 neutralizing Abs reduced the expression of TNF- and IL-6 in THP-1 cells. Furthermore, LAMPs-induced NF-B activation was increased in 293T cells transfected TLR2 plasmid. The activity of NF-B was synergically augmented by cotransfected TLR1, TLR6 and CD14 respectively. Additionally, LAMPs was shown to inhibited NF-B expression by the cotransfection with DN-MyD88 and TLR2 plasmid. These results suggest that M. genitalium-derived LAMPs can activate NF-B via TLR2/TLR1/TLR6 and CD14 in MyD88-dependent pathway.