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Approaches for the identification of potential excreted/secreted proteins of Leishmania major parasites

Published online by Cambridge University Press:  03 January 2006

M. CHENIK ,
S. LAKHAL ,
N. BEN KHALEF ,
L. ZRIBI ,
H. LOUZIR  and
K. DELLAGI
M. CHENIK
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
S. LAKHAL
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
N. BEN KHALEF
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
L. ZRIBI
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
H. LOUZIR
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
K. DELLAGI
Affiliation:
WHO Collaborating Center for Research and Training in Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002 Tunis-Belvédére, Tunisia
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Abstract

Leishmania parasites are able to survive in host macrophages despite the harsh phagolysosomal vacuoles conditions. This could reflect, in part, their capacity to secrete proteins that may play an essential role in the establishment of infection and serve as targets for cellular immune responses. To characterize Leishmania major proteins excreted/secreted early after promastigote entry into the host macrophage, we have generated antibodies against culture supernatants of stationary-phase promastigotes collected 6 h after incubation in conditions that partially reproduce those prevailing in the parasitophorous vacuole. The screening of an L. major cDNA library with these antibodies led us to isolate 33 different cDNA clones that we report here. Sequence analysis revealed that the corresponding proteins could be classified in 3 groups: 9 proteins have been previously described as excreted/secreted in Leishmania and/or other species; 11 correspond to known proteins already characterized in Leishmania and/or other species although it is unknown whether they are excreted/secreted and 13 code for unknown proteins. Interestingly, the latter are transcribed as shown by RT-PCR and some of them are stage regulated. The L. major excreted/secreted proteins may constitute putative virulence factors, vaccine candidates and/or new drug targets.

Keywords

Leishmania majorexcreted/secreted proteinsvirulencedrug targetvaccine candidatesgene expression
Type
Research Article
Information
Parasitology , Volume 132 , Issue 4 , April 2006 , pp. 493 - 509
Copyright
2006 Cambridge University Press

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References

REFERENCES

Akopyants, N. S., Matlib, R. S., Bukanova, E. N., Smeds, M. R., Brownstein, B. H., Stormo, G. D. and Beverley, S. M. ( 2004). Expression profiling using random genomic DNA microarrays identifies differentially expressed genes associated with three major developmental stages of the protozoan parasite Leishmania major. Molecular and Biochemical Parasitology 136, 71–86.CrossRefGoogle Scholar
Alexander, J., Coombs, G. H. and Mottram, J. C. ( 1998). Leishmania mexiana cysteine proteinase-deficient mutants have attenuated virulence for mice and potentiate a Th1 response. Journal of Immunology 161, 6794–6801.Google Scholar
Alexander, J. and Russell, D. G. ( 1992). The interaction of Leishmania species with macrophages. Advances in Parasitology 31, 175–254.CrossRefGoogle Scholar
Amer, A. O. and Swanson, M. S. ( 2002). A phagosome of one's own: a microbial guide to life in the macrophage. Current Opinion in Microbiology 5, 56–61.CrossRefGoogle Scholar
Barankiewicz, J., Dosch, H. M. and Cohen, A. ( 1988). Extracellular nucleotide catabolism in human B and T lymphocytes. The source of adenosine production. The Journal of Biological Chemistry 263, 7094–7098.Google Scholar
Bates, P. A., Gottlieb, M. and Dwyer, D. M. ( 1988). Leishmania donovani: identification of glycoproteins released by promastigotes during growth in vitro. Experimental Parasitology 67, 199–209.CrossRefGoogle Scholar
Ben Achour, Y., Chenik, M., Louzir, H. and Dellagi, K. ( 2002). Identification of a disulfide isomerase protein of Leishmania major as a putative virulence factor. Infection and Immunity 70, 3576–3585.CrossRefGoogle Scholar
Bendtsen, J. D., Jensen, L. J., Blom, N., Von Heijne, G. and Brunak, S. ( 2004). Feature-based prediction of non-classical and leaderless protein secretion. Protein Engineering, Design and Selection 17, 349–356.CrossRefGoogle Scholar
Berberich, C., Ramirez-Pineda, J. R., Hambrecht, C., Alber, G., Skeiky, Y. A. and Moll, H. ( 2003). Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens. Journal of Immunology 170, 3171–3179.CrossRefGoogle Scholar
Bertholet, S., Debrabant, A., Desjardins, M. and Sacks, D. ( 2005). CD8+ T cells and cross-presentation pathways in Leishmaniasis. In Third World Congress on Leishmaniosis, 10–15 April 2005, Palermo-Terrasini, Sicily, Italy.
Bousoffara, T., Louzir, H., Ben Salah, A. and Dellagi, K. ( 2004). Analysis of granzyme B activity as a surrogate marker of Leishmania-specific cell-mediated cytotoxicity in zoonotic cutaneous leishmaniasis. Journal of Infectious Diseases 189, 1265–1273.CrossRefGoogle Scholar
Brooks, D. R., Tetley, L., Coombs, G. H. and Mottram, J. C. ( 2000). Processing and trafficking of cysteine proteases in Leishmania mexicana. Journal of Cell Science 113, 4035–4041.Google Scholar
Browne, G. J. and Proud, C. G. ( 2002). Regulation of peptide-chain elongation in mammalian cells. European Journal of Biochemistry 269, 5360–5368.CrossRefGoogle Scholar
Buxbaum, L. U., Denise, H., Coombs, G. H., Alexander, J., Mottram, J. C. and Scott, P. ( 2003). Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunity. Journal of Immunology 171, 3711–3717.CrossRefGoogle Scholar
Campbell, K., Diao, H., Ji, J. and Soong, L. ( 2003). DNA immunization with the gene encoding P4 nuclease of Leishmania amazonensis protects mice against cutaneous Leishmaniasis. Infection and Immunity 71, 6270–6278.CrossRefGoogle Scholar
Cao, Y., Matsumoto, T., Motomura, K., Ohtsuru, A., Yamashita, S. and Kosaka, M. ( 1998). Impaired induction of heat shock protein implicated in decreased thermotolerance in a temperature-sensitive multinucleated cell line. Pflügers Archiv 437, 15–20.CrossRefGoogle Scholar
Carrero, J. C., Petrossian, P., Acosta, E., Sanchez-Zerpa, M., Ortiz-Ortiz, L. and Laclette, J. P. ( 2000). Cloning and characterization of Entamoeba histolytica antigens recognized by human secretory IgA antibodies. Parasitology Research 86, 330–334.CrossRefGoogle Scholar
Collins, P. R., Stack, C. M., O'Neill, S. M., Doyle, S., Ryan, T., Brennan, G. P., Mousley, A., Stewart, M., Maule, A. G., Dalton, J. P. and Donnelly, S. ( 2004). Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence: propeptide cleavage sites and autoactivation of the zymogen secreted from gastrodermal cells. The Journal of Biological Chemistry 279, 17038–17046.CrossRefGoogle Scholar
Condeelis, J. ( 1995). Elongation factor 1 alpha, translation and the cytoskeleton. Trends in Biochemical Sciences 20, 169–170.CrossRefGoogle Scholar
Cornelissen, J. B., Gaasenbeek, C. P., Borgsteede, F. H., Holland, W. G., Harmsen, M. M. and Boersma, W. J. ( 2001). Early immunodiagnosis of fasciolosis in ruminants using recombinant Fasciola hepatica cathepsin L-like protease. International Journal for Parasitology 31, 728–737.CrossRefGoogle Scholar
Cunningham, A. C. ( 2002). Parasitic adaptive mechanisms in infection by Leishmania. Experimental and Molecular Pathology 72, 132–141.CrossRefGoogle Scholar
Dalton, J. P., Neill, S. O., Stack, C., Collins, P., Walshe, A., Sekiya, M., Doyle, S., Mulcahy, G., Hoyle, D., Khaznadji, E., Moire, N., Brennan, G., Mousley, A., Kreshchenko, N., Maule, A. G. and Donnelly, S. M. ( 2003). Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines. International Journal for Parasitology 33, 1173–1181.CrossRefGoogle Scholar
Daryani, A., Hosseini, A. Z. and Dalimi, A. ( 2003). Immune responses against excreted/secreted antigens of Toxoplasma gondii tachyzoites in the murine model. Veterinary Parasitology 113, 123–134.CrossRefGoogle Scholar
De Carvalho, L. P., Soto, M., Jeronimo, S., Dondji, B., Bacellar, O., Luz, V., Orge Orge, G., Alonso, C., Jesus, A. R. and Carvalho, E. M. ( 2003). Characterization of the immune response to Leishmania infantum recombinant antigens. Microbes and Infection 5, 7–12.CrossRefGoogle Scholar
Delgado, G., Parra-Lopez, C. A., Vargas, L. E., Hoya, R., Estupinan, M., Guzman, F., Torres, A., Alonso, C., Velez, I. D., Spinel, C. and Patarroyo, M. E. ( 2003). Characterizing cellular immune response to kinetoplastid membrane protein-11 (KMP-11) during Leishmania (Viannia) panamensis infection using dendritic cells (DCs) as antigen presenting cells (APCs). Parasite Immunology 25, 199–209.CrossRefGoogle Scholar
Denise, H., Mcneil, K., Brooks, D. R., Alexander, J., Coombs, G. H. and Mottram, J. C. ( 2003). Expression of multiple CPB genes encoding cysteine proteases is required for Leishmania mexicana virulence in vivo. Infection and Immunity 71, 3190–3195.CrossRefGoogle Scholar
Desjeux, P. ( 1996). Leishmaniasis. Public health aspects and control. Clinics in Dermatology 14, 417–423.CrossRefGoogle Scholar
Dobbin, C. A., Smith, N. C. and Johnson, A. M. ( 2002). Heat shock protein 70 is a potential virulence factor in murine toxoplasma infection via immunomodulation of host NF-kappa B and nitric oxide. Journal of Immunology 169, 958–965.CrossRefGoogle Scholar
Dowd, A. J., Smith, A. M., Mcgonigle, S. and Dalton, J. P. ( 1994). Purification and characterisation of a second cathepsin L proteinase secreted by the parasitic trematode Fasciola hepatica. European Journal of Biochemistry 223, 91–98.CrossRefGoogle Scholar
Duclos, S. and Desjardins, M. ( 2000). Subversion of a young phagosome: the survival strategies of intracellular pathogens. Cellular Microbiology 2, 365–377.CrossRefGoogle Scholar
Ferrari, D. M. and Soling, H. D. ( 1999). The protein disulphide-isomerase family: unravelling a string of folds. The Biochemical Journal 339, 1–10.Google Scholar
Garlapati, S., Dahan, E. and Shapira, M. ( 1999). Effect of acidic pH on heat shock gene expression in Leishmania. Molecular and Biochemical Parasitology 100, 95–101.CrossRefGoogle Scholar
Garrido, C., Schmitt, E., Cande, C., Vahsen, N., Parcellier, A. and Kroemer, G. ( 2003). HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2, 579–584.CrossRefGoogle Scholar
Geldhof, P., Vercauteren, I., Knox, D., Demaere, V., Van Zeveren, A., Berx, G., Vercruysse, J. and Claerebout, E. ( 2003). Protein disulphide isomerase of Ostertagia ostertagi: an excretory-secretory product of L4 and adult worms? International Journal for Parasitology 33, 129–136.Google Scholar
Handman, E. ( 1999). Cell biology of Leishmania. Advances in Parasitology 44, 1–39.CrossRefGoogle Scholar
Handman, E., Osborn, A. H., Symons, F., Van Driel, R. and Cappai, R. ( 1995 a). The Leishmania promastigote surface antigen 2 complex is differentially expressed during the parasite life cycle. Molecular and Biochemical Parasitology 74, 189–200.Google Scholar
Handman, E., Symons, F. M., Baldwin, T. M., Curtis, J. M. and Scheerlinck, J. P. ( 1995 b). Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response. Infection and Immunity 63, 4261–4267.Google Scholar
Harmsen, M. M., Cornelissen, J. B., Buijs, H. E., Boersma, W. J., Jeurissen, S. H. and Van Milligen, F. J. ( 2004). Identification of a novel Fasciola hepatica cathepsin L protease containing protective epitopes within the propeptide. International Journal for Parasitology 34, 675–682.CrossRefGoogle Scholar
Heid, C. A., Stevens, J., Livak, K. J. and Williams, P. M. ( 1996). Real time quantitative PCR. Genome Research 6, 986–994.CrossRefGoogle Scholar
Houde, M., Bertholet, S., Gagnon, E., Brunet, S., Goyette, G., Laplante, A., Princiotta, M. F., Thibault, P., Sacks, D. and Desjardins, M. ( 2003). Phagosomes are competent organelles for antigen cross-presentation. Nature 425, 402–406.CrossRefGoogle Scholar
Huang, J., Huang, Q., Zhou, X., Shen, M. M., Yen, A., Yu, S. X., Dong, G., Qu, K., Huang, P., Anderson, E. M., Daniel-Issakani, S., Buller, R. M., Payan, D. G. and Lu, H. H. ( 2004). The poxvirus p28 virulence factor is an E3 ubiquitin ligase. The Journal of Biological Chemistry 279, 54110–54116.CrossRefGoogle Scholar
Hunter-Lavin, C., Davies, E. L., Bacelar, M. M., Marshall, M. J., Andrew, S. M. and Williams, J. H. ( 2004). Hsp70 release from peripheral blood mononuclear cells. Biochemical and Biophysical Research Communications 324, 511–517.CrossRefGoogle Scholar
Imai, A., Matsuyama, T., Hanzawa, Y., Akiyama, T., Tamaoki, M., Saji, H., Shirano, Y., Kato, T., Hayashi, H., Shibata, D., Tabata, S., Komeda, Y. and Takahashi, T. ( 2004). Spermidine synthase genes are essential for survival of Arabidopsis. Plant Physiology 135, 1565–1573.CrossRefGoogle Scholar
Jardim, A., Funk, V., Caprioli, R. M. and Olafson, R. W. ( 1995). Isolation and structural characterization of the Leishmania donovani kinetoplastid membrane protein-11, a major immunoreactive membrane glycoprotein. The Biochemical Journal 305, 307–313.CrossRefGoogle Scholar
Jensen, A. T., Gasim, S., Ismail, A., Gaafar, A., Kurtzhals, J. A., Kemp, M., El Hassan, A. M., Kharazmi, A. and Theander, T. G. ( 1998). Humoral and cellular immune responses to synthetic peptides of the Leishmania donovani kinetoplastid membrane protein-11. Scandinavian Journal of Immunology 48, 103–109.CrossRefGoogle Scholar
Jimenez-Ruiz, A., Boceta, C., Bonay, P., Requena, J. M. and Alonso, C. ( 1998). Cloning, sequencing, and expression of the PSA genes from Leishmania infantum. European Journal of Biochemistry 251, 389–397.CrossRefGoogle Scholar
Kaiser, A. E., Gottwald, A. M., Wiersch, C. S., Maier, W. A. and Seitz, H. M. ( 2003). Spermidine metabolism in parasitic protozoa – a comparison to the situation in prokaryotes, viruses, plants and fungi. Folia Parasitologica 50, 3–18.CrossRefGoogle Scholar
Kebaier, C., Louzir, H., Chenik, M., Ben Salah, A. and Dellagi, K. ( 2001). Heterogeneity of wild Leishmania major isolates in experimental murine pathogenicity and specific immune response. Infection and Immunity 69, 4906–4915.CrossRefGoogle Scholar
Kedzierski, L., Montgomery, J., Bullen, D., Curtis, J., Gardiner, E., Jimenez-Ruiz, A. and Handman, E. ( 2004). A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3. Journal of Immunology 172, 4902–4906.CrossRefGoogle Scholar
Kemp, M., Handman, E., Kemp, K., Ismail, A., Mustafa, M. D., Kordofani, A. Y., Bendtzen, K., Kharazmi, A. and Theander, T. G. ( 1998). The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major. FEMS Immunology and Medical Microbiology 20, 209–218.CrossRefGoogle Scholar
Kumar, P., Pai, K., Tripathi, K., Pandey, H. P. and Sundar, S. ( 2002). Immunoblot analysis of the humoral immune response to Leishmania donovani polypeptides in cases of human visceral leishmaniasis: its usefulness in prognosis. Clinical and Diagnostic Laboratory Immunology 9, 1119–1123.CrossRefGoogle Scholar
Kurar, E. and Splitter, G. A. ( 1997). Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response. Vaccine 15, 1851–1857.CrossRefGoogle Scholar
Lalmanach, G., Boulange, A., Serveau, C., Lecaille, F., Scharfstein, J., Gauthier, F. and Authie, E. ( 2002). Congopain from Trypanosoma congolense: drug target and vaccine candidate. Biological Chemistry 383, 739–749.CrossRefGoogle Scholar
Landfear, S. M. and Ignatushchenko, M. ( 2001). The flagellum and flagellar pocket of trypanosomatids. Molecular and Biochemical Parasitology 115, 1–17.CrossRefGoogle Scholar
Lee, E. G., Kim, J. H., Shin, Y. S., Shin, G. W., Kim, Y. H., Kim, G. S., Kim, D. Y., Jung, T. S. and Suh, M. D. ( 2004). Two-dimensional gel electrophoresis and immunoblot analysis of Neospora caninum tachyzoites. Journal of Veterinary Science 5, 139–145.Google Scholar
Lei, B., Mackie, S., Lukomski, S. and Musser, J. M. ( 2000). Identification and immunogenicity of group A Streptococcus culture supernatant proteins. Infection and Immunity 68, 6807–6818.CrossRefGoogle Scholar
Lemesre, J. L., Holzmuller, P., Cavaleyra, M., Goncalves, R. B., Hottin, G. and Papierok, G. ( 2005). Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secreted antigens of Leishmania infantum promastigotes. Vaccine 23, 2825–2840.CrossRefGoogle Scholar
Len, A. C., Cordwell, S. J., Harty, D. W. and Jacques, N. A. ( 2003). Cellular and extracellular proteome analysis of Streptococcus mutans grown in a chemostat. Proteomics 3, 627–646.CrossRefGoogle Scholar
Liao, X., Ying, T., Wang, H., Wang, J., Shi, Z., Feng, E., Wei, K., Wang, Y., Zhang, X., Huang, L., Su, G. and Huang, P. ( 2003). A two-dimensional proteome map of Shigella flexneri. Electrophoresis 24, 2864–2882.CrossRefGoogle Scholar
Louzir, H., Bousoffara, T., Ben Salah, A., Kaabi, B., Chlif, S., Tak, P. P., Smeets, T. J. and Dellagi, K. ( 2005). Leishmania specific cytotoxic cellulalr immune response as a new correlate for human protection against infection. In Third World Congress on Leishmaniosis, 10–15 April 2005, Palermo-Terrasini, Sicily, Italy.
Louzir, H., Melby, P. C., Ben Salah, A., Marrakchi, H., Aoun, K., Ben Ismail, R. and Dellagi, K. ( 1998). Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major. Journal of Infectious Diseases 177, 1687–1695.CrossRefGoogle Scholar
Lovelace, J. K. and Gottlieb, M. ( 1986). Comparison of extracellular acid phosphatases from various isolates of Leishmania. The American Journal of Tropical Medicine and Hygiene 35, 1121–1128.CrossRefGoogle Scholar
Matlashewski, G. ( 2001). Leishmania infection and virulence. Medical Microbiology and Immunology 190, 37–42.CrossRefGoogle Scholar
Mattow, J., Schaible, U. E., Schmidt, F., Hagens, K., Siejak, F., Brestrich, G., Haeselbarth, G., Muller, E. C., Jungblut, P. R. and Kaufmann, S. H. ( 2003). Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Electrophoresis 24, 3405–3420.Google Scholar
Mayer, M. P. and Bukau, B. ( 2005). Hsp70 chaperones: cellular functions and molecular mechanism. Cellular and Molecular Life Sciences 62, 670–684.CrossRefGoogle Scholar
Mendez, S., Belkaid, Y., Seder, R. A. and Sacks, D. ( 2002). Optimization of DNA vaccination against cutaneous leishmaniasis. Vaccine 20, 3702–3708.CrossRefGoogle Scholar
Mottram, J. C., Coombs, G. H. and Alexander, J. ( 2004). Cysteine peptidases as virulence factors of Leishmania. Current Opinion in Microbiology 7, 375–381.CrossRefGoogle Scholar
Mottram, J. C., Souza, A. E., Hutchison, J. E., Carter, R., Frame, M. J. and Coombs, G. H. ( 1996). Evidence from disruption of the Imcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proceedings of the National Academy of Sciences, USA 93, 6008–6013.CrossRefGoogle Scholar
Mukhopadhyay, S., Sen, P., Majumder, H. K. and Roy, S. ( 1998). Reduced expression of lipophosphoglycan (LPG) and kinetoplastid membrane protein (KMP)-11 in Leishmania donovani promastigotes in axenic culture. The Journal of Parasitology 84, 644–647.CrossRefGoogle Scholar
Mustafa, A. S. ( 2002). Development of new vaccines and diagnostic reagents against tuberculosis. Molecular Immunology 39, 113–119.CrossRefGoogle Scholar
Nagano, I., Pei, F., Wu, Z., Wu, J., Cui, H., Boonmars, T. and Takahashi, Y. ( 2004). Molecular expression of a cysteine proteinase of Clonorchis sinensis and its application to an enzyme-linked immunosorbent assay for immunodiagnosis of clonorchiasis. Clinical and Diagnostic Laboratory Immunology 11, 411–416.CrossRefGoogle Scholar
Nandan, D., Cherkasov, A., Sabouti, R., Yi, T. and Reiner, N. E. ( 2003). Molecular cloning, biochemical and structural analysis of elongation factor-1 alpha from Leishmania donovani: comparison with the mammalian homologue. Biochemical and Biophysical Research Communications 302, 646–652.CrossRefGoogle Scholar
Nandan, D. and Reiner, N. E. ( 2005). Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1. Clinical Immunology 114, 266–277.CrossRefGoogle Scholar
Nandan, D., Yi, T., Lopez, M., Lai, C. and Reiner, N. E. ( 2002). Leishmania EF-1 alpha activates the Src homology 2 domain containing tyrosine phosphatase SHP-1 leading to macrophage deactivation. The Journal of Biological Chemistry 277, 50190–50197.CrossRefGoogle Scholar
Nishisaka, M., Yokoyama, N., Xnan, X., Inoue, N., Nagasawa, H., Fujisaki, K., Mikami, T. and Igarashi, I. ( 2001). Characterisation of the gene encoding a protective antigen from Babesia microti identified it as eta subunit of chaperonin containing T-complex protein 1. International Journal for Parasitology 31, 1673–1679.CrossRefGoogle Scholar
Ouaissi, A., Ouaissi, M., Tavares, J. and Cordeiro-Da-Silva, A. ( 2004). Host Cell Phenotypic Variability Induced by Trypanosomatid-Parasite-Released Immunomodulatory Factors: Physiopathological Implications. Journal of Biomedicine and Biotechnology 2004, 167–174.CrossRefGoogle Scholar
Planelles, L., Thomas, M. C., Alonso, C. and Lopez, M. C. ( 2001). DNA immunization with Trypanosoma cruzi HSP70 fused to the KMP11 protein elicits a cytotoxic and humoral immune response against the antigen and leads to protection. Infection and Immunity 69, 6558–6563.CrossRefGoogle Scholar
Pockley, A. G., Shepherd, J. and Corton, J. M. ( 1998). Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunological Investigations 27, 367–377.CrossRefGoogle Scholar
Pontes, D. S., Dorella, F. A., Ribeiro, L. A., Miyoshi, A., Le Loir, Y., Gruss, A., Oliveira, S. C., Langella, P. and Azevedo, V. ( 2003). Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen. Journal of Drug Targeting 11, 489–493.CrossRefGoogle Scholar
Prigione, I., Facchetti, P., Lecordier, L., Deslee, D., Chiesa, S., Cesbron-Delauw, M. F. and Pistoia, V. ( 2000). T cell clones raised from chronically infected healthy humans by stimulation with Toxoplasma gondii excretory-secretory antigens cross-react with live tachyzoites: characterization of the fine antigenic specificity of the clones and implications for vaccine development. Journal of Immunology 164, 3741–3748.CrossRefGoogle Scholar
Probst, P., Stromberg, E., Ghalib, H. W., Mozel, M., Badaro, R., Reed, S. G. and Webb, J. R. ( 2001). Identification and characterization of T cell-stimulating antigens from Leishmania by CD4 T cell expression cloning. Journal of Immunology 166, 498–505.CrossRefGoogle Scholar
Pym, A. S., Brodin, P., Majlessi, L., Brosch, R., Demangel, C., Williams, A., Griffiths, K. E., Marchal, G., Leclerc, C. and Cole, S. T. ( 2003). Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nature, Medicine 9, 533–539.CrossRefGoogle Scholar
Rafati, S., Salmanian, A. H., Hashemi, K., Schaff, C., Belli, S. and Fasel, N. ( 2001 a). Identification of Leishmania major cysteine proteinases as targets of the immune response in humans. Molecular and Biochemical Parasitology 113, 35–43.Google Scholar
Rafati, S., Salmanian, A. H., Taheri, T., Vafa, M. and Fasel, N. ( 2001 b). A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cysteine proteinases of Leishmania major. Vaccine 19, 3369–3375.Google Scholar
Ramirez, J. R., Gilchrist, K., Robledo, S., Sepulveda, J. C., Moll, H., Soldati, D. and Berberich, C. ( 2001). Attenuated Toxoplasma gondii ts-4 mutants engineered to express the Leishmania antigen KMP-11 elicit a specific immune response in BALB/c mice. Vaccine 20, 455–461.CrossRefGoogle Scholar
Requena, J. M., Soto, M., Doria, M. D. and Alonso, C. ( 2000). Immune and clinical parameters associated with Leishmania infantum infection in the golden hamster model. Veterinary Immunology and Immunopathology 76, 269–281.CrossRefGoogle Scholar
Rico, A. I., Angel, S. O., Alonso, C. and Requena, J. M. ( 1999). Immunostimulatory properties of the Leishmania infantum heat shock proteins HSP70 and HSP83. Molecular Immunology 36, 1131–1139.CrossRefGoogle Scholar
Roberts, S. C., Jiang, Y., Jardim, A., Carter, N. S., Heby, O. and Ullman, B. ( 2001). Genetic analysis of spermidine synthase from Leishmania donovani. Molecular and Biochemical Parasitology 115, 217–226.CrossRefGoogle Scholar
Robinson, P. A. and Ardley, H. C. ( 2004). Ubiquitin-protein ligases–novel therapeutic targets? Current Protein and Peptide Science 5, 163–176.Google Scholar
Rosa, R., Rodrigues, O. R., Marques, C. and Santos-Gomes, G. M. ( 2005). Leishmania infantum: soluble proteins released by the parasite exert differential effects on host immune response. Experimental Parasitology 109, 106–114.CrossRefGoogle Scholar
Ryazanov, A. G., Rudkin, B. B. and Spirin, A. S. ( 1991). Regulation of protein synthesis at the elongation stage. New insights into the control of gene expression in eukaryotes. FEBS Letters 285, 170–175.Google Scholar
Sacks, D. L. ( 2001). Abstract Leishmania-sand fly interactions controlling species-specific vector competence. Cellular Microbiology 3, 189–196.CrossRefGoogle Scholar
Salotra, P., Raina, A. and Negi, N. S. ( 1999). Immunoblot analysis of the antibody response to antigens of Leishmania donovani in Indian kala-azar. British Journal of Biomedical Science 56, 263–267.Google Scholar
Sereno, D., Vanhille, L., Vergnes, B., Monte-Allegre, A. and Ouaissi, A. ( 2005). Experimental study of the function of the excreted/secreted Leishmania LmSIR2 protein by heterologous expression in eukaryotic cell line. Kinetoplastid Biology and Disease 4, 1.CrossRefGoogle Scholar
Shams, H., Klucar, P., Weis, S. E., Lalvani, A., Moonan, P. K., Safi, H., Wizel, B., Ewer, K., Nepom, G. T., Lewinsohn, D. M., Andersen, P. and Barnes, P. F. ( 2004). Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles. Journal of Immunology 173, 1966–1977.CrossRefGoogle Scholar
Shin, Y. S., Lee, E. G., Shin, G. W., Kim, Y. R., Lee, E. Y., Kim, J. H., Jang, H., Gershwin, L. J., Kim, D. Y., Kim, Y. H., Kim, G. S., Suh, M. D. and Jung, T. S. ( 2004). Identification of antigenic proteins from Neospora caninum recognized by bovine immunoglobulins M, E, A and G using immunoproteomics. Proteomics 4, 3600–3609.CrossRefGoogle Scholar
Smith, A. M., Dowd, A. J., Mcgonigle, S., Keegan, P. S., Brennan, G., Trudgett, A. and Dalton, J. P. ( 1993). Purification of a cathepsin L-like proteinase secreted by adult Fasciola hepatica. Molecular and Biochemical Parasitology 62, 1–8.CrossRefGoogle Scholar
Spath, G. F. and Beverley, S. M. ( 2001). A lipophosphoglycan-independent method for isolation of infective Leishmania metacyclic promastigotes by density gradient centrifugation. Experimental Parasitology 99, 97–103.CrossRefGoogle Scholar
Symons, F. M., Murray, P. J., Ji, H., Simpson, R J., Osborn, A. H., Cappai, R. and Handman, E. ( 1994). Characterization of a polymorphic family of integral membrane proteins in promastigotes of different Leishmania species. Molecular and Biochemical Parasitology 67, 103–113.CrossRefGoogle Scholar
Tanudji, M., Hevi, S. and Chuck, S. L. ( 2002). Improperly folded green fluorescent protein is secreted via a non-classical pathway. Journal of Cell Science 115, 3849–3857.CrossRefGoogle Scholar
Tonui, W. K., Mejia, J. S., Hochberg, L., Mbow, M. L., Ryan, J. R., Chan, A. S., Martin, S. K. and Titus, R. G. ( 2004). Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L. major. Infection and Immunity 72, 5654–5661.CrossRefGoogle Scholar
Turano, C., Coppari, S., Altieri, F. and Ferraro, A. ( 2002). Proteins of the PDI family: unpredicted non-ER locations and functions. Journal of Cellular Physiology 193, 154–163.CrossRefGoogle Scholar
Vercauteren, I., Geldhof, P., Peelaers, I., Claerebout, E., Berx, G. and Vercruysse, J. ( 2003). Identification of excretory-secretory products of larval and adult Ostertagia ostertagi by immunoscreening of cDNA libraries. Molecular and Biochemical Parastiology 126, 201–208.CrossRefGoogle Scholar
Voland, P., Weeks, D. L., Vaira, D., Prinz, C. and Sachs, G. ( 2002). Specific identification of three low molecular weight membrane-associated antigens of Helicobacter pylori. Aliment Pharmacology and Therapeutics 16, 533–544.CrossRefGoogle Scholar
Watt, S. A., Wilke, A., Patschkowski, T. and Niehaus, K. ( 2005). Comprehensive analysis of the extracellular proteins from Xanthomonas campestris pv. campestris B100. Proteomics 5, 153–167.CrossRefGoogle Scholar
Webb, J. R., Campos-Neto, A., Ovendale, P. J., Martin, T. I., Stromberg, E. J., Badaro, R. and Reed, S. G. ( 1998). Human and murine immune responses to a novel Leishmania major recombinant protein encoded by members of a multicopy gene family. Infection and Immunity 66, 3279–3289.Google Scholar
Wiese, M., Ilg, T., Lottspeich, F. and Overath, P. ( 1995). Ser/Thr-rich repetitive motifs as targets for phosphoglycan modifications in Leishmania mexicana secreted acid phosphatase. The EMBO Journal 14, 1067–1074.Google Scholar
Wilkinson, B. and Gilbert, H. F. ( 2004). Protein disulfide isomerase. Biochimica et Biophysica Acta 1699, 35–44.CrossRefGoogle Scholar
Yahiaoui, B., Taibi, A. and Ouaissi, A. ( 1996). A Leishmania major protein with extensive homology to silent information regulator 2 of Saccharomyces cerevisiae. Gene 169, 115–118.CrossRefGoogle Scholar
Zadeh-Vakili, A., Taheri, T., Taslimi, Y., Doustdari, F., Salmanian, A. H. and Rafati, S. ( 2004). Immunization with the hybrid protein vaccine, consisting of Leishmania major cysteine proteinases Type I (CPB) and Type II (CPA), partially protects against leishmaniasis. Vaccine 22, 1930–1940.CrossRefGoogle Scholar