The Phosphoenolpyruvate Carboxykinase of Mycobacterium Tuberculosis Induces Strong Cell-Mediated Immune Responses in Mice
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Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes guanosine or adenosine mononucleotide-dependent reversible conversion of oxaloacetate (OAA) and phosphoenolpyruvate (PEP). Mycobacterium (M) tuberculosis possesses a putative GTP-dependent PEPCK. To analyze the immune responses caused by PEPCK, the effects of PEPCK on the induction of CD4+ T cells and cytokines such as IFN-γ, IL-12 and TNF-α were evaluated in mice. It was found that the number of CD4+ T cells was increased in the PEPCK immunized mice although the change of the number of CD8+ T cells was not significant. The cytokines IFN-γ, IL-12 and TNF-α were increased significantly in the mice immunized with PEPCK than those of incomplete adjuvant. These characteristics were further demonstrated in the mice infected by pckA mutated BCG strain. The results indicate that PEPCK can effectively induce cell-mediated immune response by increasing activity of cytokines and PEPCK may be a promising new subunit vaccine candidate for tuberculosis.
KeywordsMycobacterium tuberculosis phosphoenolpyruvate carboxykinase cell immune response
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- 2.Hanson RW, Patel YM: P-Enolpyruvate carboxykinase: the gene and the enzyme. In: Meister A (Ed) Advances in Enzymology (Meister, A., ed.), John Wiley and Sons, New York, NY. pp. 203–281, 1994Google Scholar
- 8.Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CEIII, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver S, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton S, Squares S, Squares R, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393(6685): 537–544, 1998PubMedCrossRefADSGoogle Scholar
- 12.Liu K, Zhang D, Wei Q, Li J, Li G, Yu J: Biological role analysis of a surface antigen of Toxoplasma gondii. World J Gastroenterol, in impress, 2006Google Scholar
- 17.Hernandez HJ, Wang N, Tzellas MJ, Stadecker: Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni. Eur J Immunol 7: 1170–1176, 1997Google Scholar
- 18.Lyadova IV, Eruslanov EB, Khaidukov SV, Yeremeev VV, Majorov KB, Pichugin AV, Nikonenko BV, Kondratieva TK, Apt AS: Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease. J Immunol 165(10): 5921–5931, 2000PubMedGoogle Scholar
- 25.Rajavelu P, Das SD: Cell-mediated immune responses of healthy laboratory volunteers to sonicate antigens prepared from the most prevalent strains of Mycobacterium tuberculosis from South India harboring a single copy of IS6110. Clin Diagn Lab Immunol 10(6): 1149–1152, 2003PubMedCrossRefGoogle Scholar
- 32.Garcia I, Miyazaki Y, Marchal G, Lesslauer W, Vassalli P: High sensitivity of transgenic mice expressing soluble TNFR1 fusion protein to mycobacterial infections: synergistic action of TNF-α and IFN-gamma in the differentiation of protective granulomas. Eur J Immunol 27: 3182–3190, 1997PubMedGoogle Scholar