Abstract
Processing of mycobacterial antigens by immunoproteasome is necessary to control infection and to protect the organism from the development of active tuberculosis. We have investigated the activation of transcription of immunoproteasome subunit genes in peritoneal monocytes of C57Bl/6 mice infected with a vaccine M. bovis strain BCG and a virulent M. tuberculosis strain H37Rv. The level of transcription of LMP2, LMP7, and MECL1 subunits did not increase on the first and second days after a single infection. After two rounds of infection with M. bovis BCG, only the transcription of the LMP7 subunit gene was enhanced. However, the subsequent infection of monocytes, first with the vaccine strain, then with the virulent strain, resulted in a dramatic rise in the transcription of all immunoproteasome subunit genes. The transcription of the gene that encodes the PA28α subunit of the PA28 regulatory complex was activated only after a single infection of monocytes with M. bovis BCG. Thus, vaccination with M. bovis BCG promotes the efficient activation of immunoproteasomal genes in the case of subsequent contact with the virulent M. tuberculosis strain H37Rv.
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Abbreviations
- MHC:
-
major histocompatibility complex
- IFN-γ:
-
interferon γ
- TNF-α:
-
tumor necrosis factor α
References
Dye C. 2006. Global epidemiology of tuberculosis. Lancet. 367, 938–940.
Colditz G.A., Brever T.F., Berkey C.S., Wilson M.E., Burdick E., Fineberg H.V., Mosteller F. 1994. Efficacy of BCG vaccine in the prevention of tuberculosis: Meta-analysis of the published literature. J. A. Med. Assoc. 271, 698–702.
Fenton M.J. 1998. Macrophages and tuberculosis. Curr. Opin. Hematol. 5, 72–78.
McDonough K. A., Kress Y., Bloom B. R. 1993. Pathogenesis of tuberculosis: Interaction of Mycobacterium tuberculosis with macrophages. Infect. Immun. 61, 2763–2773.
Preckel T., Fung-Leung W.P., Cai Z., Vitiello A., Salter-Cid L., Winqvist O., Wolfe T.G., Von Herrath M., Angulo A., Ghazal P., Lee J.D., Fourie A.M., Wu Y., Pang J., Ngo K., Peterson P.A., Früh K., Yang Y. 1999. Impaired immunoproteasome assembly and immune response in PA28K/K mice. Science. 286, 2162–2165.
Rechsteiner M., Realini C., Ustrell V. 2000. The proteasome activator 11 S REG (PA28) and class 1 antigen presentation. Biochem. J. 345, 1–15.
Schwarz K., Eggers M., Soza A. 2000. The proteasome regulator PAa/b can enhance antigen presentation without affecting 20S proteasome subunit composition. Eur. J. Immunol. 30, 3672–3679.
Lewinsohn D.M., Grotzke J.E., Heinzel A.S., Zhu L., Ovendale P.J., Johnson M., Alderson M.R. 2006. Secreted proteins from Mycobacterium tuberculosis gain access to the cytosolic MHC class-I antigen-processing pathway. J. Immunol. 177, 437–42.
Grotzke J.E., Harriff M.J., Siler A.C., Nolt D., Delepine J., Lewinsohn D.A., Lewinsohn D.M. 2009. The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle. PLoS Pathog. 5, 1000374.
Wang D., Zhou Y., Ji L., He T., Lin F., Lin R., Lin T., Mo Y. 2012. Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China. PLoS One. 7, 33051.
Chernousova L.N., Timofeev A.V., Smirnova T.G., Karpov, V.L., Afanas’eva E.G. 2007. Ex vivo production of interferon-gamma, tumor necrosis factor-alpha, and interleukin-6 by mouse macrophages during infection with M. bovis and M. tuberculosis H37Rv. Bull. Exp. Biol. Med. 144(5), 709–712.
Flynn J.L., Chan J., Triebold K.J., Dalton D.K., Stewart T.A., Bloom B.R. 1993. An essential role for interferon γ in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178, 2249–2254.
Dalton D.K., Pitts-Meek S., Keshav S., Figari I.S., Bradley A., Stewart T.A. 1993. Multiple defects of immune cell function in mice with disrupted interferon gamma genes. Science. 259, 1739–1742.
Cooper A.M., Dalton D.K., Stewart T.A., Griffin J.P., Russell D.G., Orme I.M. 1993. Disseminated tuberculosis in interferon γ gene-disrupted mice. J. Exp. Med. 178, 2243–2247.
Banaiee N., Kincaid E.Z., Buchwald U., Jacobs W.R., Jr., Ernst J.D. 2006. Potent inhibition of macrophage responses to IFN-γ by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J. Immunol. 176, 3019–3027.
Ortiz-Navarrete V., Seelig A., Gernold M., Frentzel S., Kloetzel P.M., Hammerling G.J. 1991. Subunit of the ‘20S’ proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature. 353, 662–664.
Yang Y., Waters J.B., Fruh K., Peterson P.A. 1992. Proteasomes are regulated by interferon gamma: Implications for antigen processing. Proc. Natl. Acad. Sci. U. S. A. 89. 4928–4932.
Dubiel W., Pratt G., Ferrell K., Rechsteiner M. 1994. Purification of a 11S regulator of the multicatalytic proteinase. J. Biol. Chem. 267, 22369–22377.
Ma C.P., Slaugther C.A., DeMartino G.N. 1992. Identification, purification, and characterisation of a protein activator (PA28) of the 20S proteasome (macropain). J. Biol. Chem. 267, 10515–10523.
van den Eynde B.J., Morel S. 2001. Different processing of class-1-restricted epitopes by the standard proteasome and immunoproteasome. Curr. Opin. Immunol. 13, 147–153.
Hendil K.B., Khan S., Tanaka K. 1998. Simultaneous binding of PA28 and PA700 activators to 20S proteasomes. Biochem. J. 332, 749–754.
Sharova N.P. 2006. Immune proteasomes and immunity. Russ. J. Dev. Biol. 37(3), 139–145.
Neyrolles O., Gould K., Gares M.P., Brett S., Janssen R., O’Gaora P., Herrmann J.L., Prévost M.C., Perret E., Thole J.E., Young D. 2001. Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria. J. Immunol. 166, 447–457.
Schaible U.E., Winau F., Sieling P.A., Fischer K., Collins H.L., Hagens K., Modlin R.L., Brinkmann V., Kaufmann S.H. 2003. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nature Med. 9, 1039–1046.
Molloy A., Laochumroonvorapong P., Kaplan G. 1994. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus. J. Exp. Med. 180, 1499–1509.
Flesch I.E., Hess J.H., Huang S., Aguet M., Rothe J., Bluethmann H., Kaufmann S.H. 1995. Early IL-12 production by macrophages in response to mycobacterial infection depends on IF and TNF. J. Exp. Med. 181, 1615–1621.
Groettrup M., Standera S., Stohwasser R., Kloetzel P.-M. 1997. The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome. Proc. Natl. Acad. Sci. U. S. A. 94, 8970–8975.
Griffin T.A., Nandi D., Cruz M., Fehling H.J., van Kaer L., Monaco J.J., Colbert A. 1998. Immunoproteasome assembly: Cooperative incorporation of interferon γ (IFNγ)-inducible subunits. J. Exp. Med. 187, 97–104.
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Original Russian Text © A.V. Timofeev, Yu.V. Kuzmenko, I.I. Zharkova, E.S. Starodubova, V. L. Karpov, 2013, published in Molekulyarnaya Biologiya, 2013, Vol. 47, No. 2, pp. 311–316.
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Timofeev, A.V., Kuzmenko, Y.V., Zharkova, I.I. et al. Activation of transcription of immunoproteasome subunit genes in murine monocytes infected with different mycobacterial strains. Mol Biol 47, 275–279 (2013). https://doi.org/10.1134/S0026893313020155
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DOI: https://doi.org/10.1134/S0026893313020155