Xiao LIan Zhang, Lingyun Zhang and Huan Xiong
Wuhan University, China
Posters & Accepted Abstracts: J Microb Biochem Technol
Tuberculosis (TB) is a major global health problem. Overall, approximately one-third of the world�??s population is currently asymptomatically infected with Mycobacterium tuberculosis (M. tb), the etiological agent of TB. In recent years, comparative genomic studies using subtractive DNA hybridization and DNA microarray have identified >100 open reading frames (ORFs) distributed in several M. tb-specific genomic regions of difference, designated RD1 to RD16. These are absent in BCG and M. bovis, suggesting that the RD-encoded proteins may be virulent factors for TB pathogenicity and associated immune responses. Here after screening RDs recombinant proteins, we found a Rv3873 recombinant protein from RD1 could induce early and late apoptosis in mouse peritoneal macrophages. Rv3873 caused macrophages death independent of TLR2/4, MYD88 and IL-6. Using GST-Pulldown, Mass Spectrometry and Western blot experiments; we found that Rv3873 interacted with H2A protein of macrophages. Dual luciferase reporter assay and western blot assay showed that Rv3873 could down regulate the NF-kappa B transcription, inhibit the phosphorylation�??s of p-P65, p-JNK and p-ERK, thus further inhibited macrophage early (15-60 minutes) expression of inflammatory factor TNF-alpha. TNF-alpha is an important immune regulatory molecule in anti-tuberculosis immune response. Our data suggest that the inhibition of the expression of TNF-alpha by Rv3873 may promote the progression of tuberculosis. Rv3873 may be as a negative immune regulate factor contributing to TB pathogenesis.