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J Bacteriol Virol. 2009 Sep;39(3):183-193. English. In Vitro.
Kim SY , Shin AR , Lee BS , Kim HJ , Jeon BY , Cho SN , Park JK , Shin SJ .
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Cancer Research Institute, College of Medicine, Chungnam National University, Daejeon, Korea.
Infectious Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, Korea.
Department of Microbiology and Brain Korea 21 Project for Medical Science, Yonsei Univeristy College of Medicine, Seoul, Korea.

Tuberculosis, which is caused by Mycobacterium tuberculosis (M. tb), is one of the most important infectious diseases in the world. Although many functional studies have been conducted on M. tb proteins in the post-genomic era, little is known about the function of many proteins expressed specifically during latency. Previously, we reported that Rv2041c from M. tb H37Rv is highly expressed under conditions of low pH and hypoxia, which represent the in vitro mimicry of latent tuberculosis. In the present study, increased expression levels of Rv2041c under hypoxia and low pH in vitro culture was confirmed by RT-PCR. Interestingly, Rv2041c showed significantly increased expression among genes of the same operon and genes belonging to the same functional group. Finally, the immune responses elicited by the recombinant (r) Rv2041c protein were investigated using ex vivo and in vivo models of M. tb infection. A significantly high level of pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-12p40 was detected in a dose-dependent manner by treatment of murine bone marrow-derived macrophages with rRv2041c protein. In addition, IFN-gamma and TNF-alpha secretion increased after stimulation with purified Rv2041c protein to lymphocytes from latent and active TB mice in a modified Cornell model. In conclusion, our findings suggest that Rv2041c is a new T-cell antigen and could be a potential vaccine candidate against M. tb infection by inducing a strong cellular immune response.

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