title: Mycobacterium tuberculosis Rv2882c Protein Induces Activation of Macrophages through TLR4 and Exhibits Vaccine Potential.
abstract: Macrophages constitute the first line of defense against Mycobacterium tuberculosis and are critical in linking innate and adaptive immunity. Therefore, the identification and characterization of mycobacterial proteins that modulate macrophage function are essential for understanding tuberculosis pathogenesis. In this study, we identified the novel macrophage-activating protein, Rv2882c, from M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and major histocompatibility complex molecules via Toll-like receptor 4, myeloid differentiation primary response protein 88, and Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta. Mitogen-activated protein kinases and NF-κB signaling pathways were involved in Rv2882c-induced macrophage activation. Further, Rv2882c-treated macrophages induced expansion of the effector/memory T cell population and Th1 immune responses. In addition, boosting Bacillus Calmette-Guerin vaccination with Rv2882c improved protective efficacy against M. tuberculosis in our model system. These results suggest that Rv2882c is an antigen that could be used for tuberculosis vaccine development.
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Han-Gyu
authors.initials: HG
authors.lastname: Choi
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Seunga
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Back
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Hye-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Hyun Shik
authors.initials: HS
authors.lastname: Bae
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Chul Hee
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D032581:Tuberculosis Vaccines; D020928:Mitogen-Activated Protein Kinases