Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-18T18:40:10.793Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunological consequences of stress-related proteins – cytosolic tryparedoxin peroxidase and chaperonin TCP20 – identified in splenic amastigotes of Leishmania donovani as Th1 stimulatory, in experimental visceral leishmaniasis

Published online by Cambridge University Press:  11 December 2014

ANIL KUMAR JAISWAL ,
PRASHANT KHARE ,
SUMIT JOSHI ,
KEERTI RAWAT ,
NARENDRA YADAV ,
SHYAM SUNDAR  and
ANURADHA DUBE
ANIL KUMAR JAISWAL
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
PRASHANT KHARE
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
SUMIT JOSHI
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
KEERTI RAWAT
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
NARENDRA YADAV
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
SHYAM SUNDAR
Affiliation:
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
ANURADHA DUBE*
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India
*
* Corresponding author. Division of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India. E-mail: [email protected], [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

In earlier studies, proteomic characterization of splenic amastigote fractions from clinical isolates of Leishmania donovani, exhibiting significant cellular responses in cured Leishmania subjects, led to the identification of cytosolic tryparedoxin peroxidase (LdcTryP) and chaperonin-TCP20 (LdTCP20) as Th1-stimulatory proteins. Both the proteins, particularly LdTCP20 for the first time, were successfully cloned, overexpressed, purified and were found to be localized in the cytosol of purified splenic amastigotes. When evaluated against lymphocytes of cured Leishmania-infected hamsters, the purified recombinant proteins (rLdcTryP and rLdTCP20) induced their proliferations as well as nitric oxide production. Similarly, these proteins also generated Th1-type cytokines (IFN-γ/IL-12) from stimulated PBMCs of cured/endemic Leishmania patients. Further, vaccination with rLdcTryP elicited noticeable delayed-type hypersensitivity response and offered considerably good prophylactic efficacy (~78% inhibition) against L. donovani challenge in hamsters, which was well supported by the increased mRNA expression of Th1 and Th2 cytokines. However, animals vaccinated with rLdTCP20 exhibited comparatively lesser prophylactic efficacy (~55%) with inferior immunological response. The results indicate the potentiality of rLdcTryP protein, between the two, as a suitable anti-leishmanial vaccine. Since, rLdTCP20 is also an important target, for optimization, further attempts towards determination of immunodominant regions for designing fusion peptides may be taken up.

Keywords

Leishmania donovanisplenic amastigotecytosolic tryparedoxin peroxidasechaperonin TCP20immunogenicitycured Leishmania patients/hamstersprophylactic efficacycellular immune response
Type
Research Article
Information
Parasitology , Volume 142 , Issue 5 , April 2015 , pp. 728 - 744
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Afrin, F., Rajesh, R., Anam, K., Gopinath, M., Pal, S. and Ali, N. (2002). Characterization of Leishmania donovani antigens encapsulated in liposomes that induce protective immunity in BALB/c mice. Infection and Immunity 70, 6697–6706.CrossRefGoogle ScholarPubMed
Ahmed, S. B., Bahloul, C., Robbana, C., Askri, S. and Dellagi, K. (2004). A comparative evaluation of different DNA vaccine candidates against experimental murine leishmaniasis due to L. major. Vaccine 22, 1631–1639.CrossRefGoogle ScholarPubMed
Albuquerque, L. C., Mendonca, I. R., Cardoso, P. N., Baldacara, L. R., Borges, M. R., Borges Jda, C. and Pranchevicius, M. C. (2014). HIV/AIDS-related visceral leishmaniasis: a clinical and epidemiological description of visceral leishmaniasis in northern Brazil. Rev Soc Bras Med Trop 47, 38–46.CrossRefGoogle ScholarPubMed
Alvar, J., Aparicio, P., Aseffa, A., Den Boer, M., Canavate, C., Dedet, J. P., Gradoni, L., Ter Horst, R., Lopez-Velez, R. and Moreno, J. (2008). The relationship between leishmaniasis and AIDS: the second 10 years. Clinical Microbiology Reviews 21, 334–359.CrossRefGoogle ScholarPubMed
Alvar, J., Velez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J. and den Boer, M. (2012). Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7, e35671.CrossRefGoogle ScholarPubMed
Armijos, R. X., Weigel, M. M., Calvopina, M., Hidalgo, A., Cevallos, W. and Correa, J. (2004). Safety, immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis. Vaccine 22, 1320–1326.CrossRefGoogle ScholarPubMed
Assreuy, J., Cunha, F. Q., Epperlein, M., Noronha-Dutra, A., O'Donnell, C. A., Liew, F. Y. and Moncada, S. (1994). Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major . European Journal of Immunology 24, 672–676.CrossRefGoogle ScholarPubMed
Basu, M. K. and Ray, M. (2005). Macrophage and Leishmania: an unacceptable coexistence. Critical Reviews in Microbiology 31, 145–154.CrossRefGoogle ScholarPubMed
Basu, R., Bhaumik, S., Basu, J. M., Naskar, K., De, T. and Roy, S. (2005). Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis. Journal of Immunology 174, 7160–7171.CrossRefGoogle ScholarPubMed
Bates, P. A. (1993). Axenic culture of Leishmania amastigotes. Parasitology Today 9, 143–146.CrossRefGoogle ScholarPubMed
Bhowmick, S. and Ali, N. (2009). Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PLoS One 4, e5820.CrossRefGoogle ScholarPubMed
Bhowmick, S., Ravindran, R. and Ali, N. (2007). Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response. Vaccine 25, 6544–6556.CrossRefGoogle ScholarPubMed
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Caldas, A., Favali, C., Aquino, D., Vinhas, V., van Weyenbergh, J., Brodskyn, C., Costa, J., Barral-Netto, M. and Barral, A. (2005). Balance of IL-10 and interferon-gamma plasma levels in human visceral leishmaniasis: implications in the pathogenesis. BMC Infectious Disease 5, 113.CrossRefGoogle ScholarPubMed
Carson, C., Antoniou, M., Ruiz-Arguello, M. B., Alcami, A., Christodoulou, V., Messaritakis, I., Blackwell, J. M. and Courtenay, O. (2009). A prime/boost DNA/Modified vaccinia virus Ankara vaccine expressing recombinant Leishmania DNA encoding TRYP is safe and immunogenic in outbred dogs, the reservoir of zoonotic visceral leishmaniasis. Vaccine 27, 1080–1086.CrossRefGoogle ScholarPubMed
Castro, H., Budde, H., Flohe, L., Hofmann, B., Lunsdorf, H., Wissing, J. and Tomas, A. M. (2002). Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum . Free Radical Biology Medicine 33, 1563–1574.CrossRefGoogle ScholarPubMed
Charest, H., Zhang, W. W. and Matlashewski, G. (1996). The developmental expression of Leishmania donovani A2 amastigote-specific genes is post-transcriptionally mediated and involves elements located in the 3′-untranslated region. Journal of Biological Chemistry 271, 17081–17090.CrossRefGoogle Scholar
Coelho, E. A., Tavares, C. A., Carvalho, F. A., Chaves, K. F., Teixeira, K. N., Rodrigues, R. C., Charest, H., Matlashewski, G., Gazzinelli, R. T. and Fernandes, A. P. (2003). Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection. Infection and Immunology 71, 3988–3994.CrossRefGoogle Scholar
Coelho, V. T., Oliveira, J. S., Valadares, D. G., Chavez-Fumagalli, M. A., Duarte, M. C., Lage, P. S., Soto, M., Santoro, M. M., Tavares, C. A., Fernandes, A. P. and Coelho, E. A. (2012). Identification of proteins in promastigote and amastigote-like Leishmania using an immunoproteomic approach. PLoS Neglected Tropical Disease 6, e1430.CrossRefGoogle ScholarPubMed
Collin, S., Davidson, R., Ritmeijer, K., Keus, K., Melaku, Y., Kipngetich, S. and Davies, C. (2004). Conflict and kala-azar: determinants of adverse outcomes of kala-azar among patients in southern Sudan. Clinical Infectious Disease 38, 612–619.CrossRefGoogle ScholarPubMed
Cota, G. F., de Sousa, M. R. and Rabello, A. (2011). Predictors of visceral leishmaniasis relapse in HIV-infected patients: a systematic review. PLoS Neglected Tropical Disease 5, e1153.CrossRefGoogle ScholarPubMed
Da Luz, Z. M., Pimenta, D. N., Rabello, A. and Schall, V. (2003). Evaluation of informative materials on leishmaniasis distributed in Brazil: criteria and basis for the production and improvement of health education materials. Cad Saude Publica 19, 561–569.CrossRefGoogle ScholarPubMed
Davidson, R. N. (1998). Practical guide for the treatment of leishmaniasis. Drugs 56, 1009–1018.CrossRefGoogle ScholarPubMed
Davies, C. R., Kaye, P., Croft, S. L. and Sundar, S. (2003). Leishmaniasis: new approaches to disease control. British Medical Journal 326, 377–382.CrossRefGoogle ScholarPubMed
Ding, A. H., Nathan, C. F. and Stuehr, D. J. (1988). Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. Journal of Immunology 141, 2407–2412.CrossRefGoogle ScholarPubMed
Dube, A., Singh, N. and Sundar, S. (2005). Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. Parasitology Research 96, 216–223.CrossRefGoogle Scholar
El Fakhry, Y., Ouellette, M. and Papadopoulou, B. (2002). A proteomic approach to identify developmentally regulated proteins in Leishmania infantum . Proteomics 2, 1007–1017.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Eperon, S. and McMahon-Pratt, D. (1989). Extracellular cultivation and morphological characterization of amastigote-like forms of Leishmania panamensis and L. braziliensis . Journal of Protozoology 36, 502–510.CrossRefGoogle ScholarPubMed
Farajnia, S., Mahboudi, F., Ajdari, S., Reiner, N. E., Kariminia, A. and Alimohammadian, M. H. (2005). Mononuclear cells from patients recovered from cutaneous leishmaniasis respond to Leishmania major amastigote class I nuclease with a predominant Th1-like response. Clinical and Experimental Immunology 139, 498–505.CrossRefGoogle Scholar
Fernandes, A. P., Costa, M. M., Coelho, E. A., Michalick, M. S., de Freitas, E., Melo, M. N., Luiz Tafuri, W., Resende Dde, M., Hermont, V., Abrantes Cde, F. and Gazzinelli, R. T. (2008). Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 26, 5888–5895.CrossRefGoogle ScholarPubMed
Fiorillo, A., Colotti, G., Boffi, A., Baiocco, P. and Ilari, A. (2012). The crystal structures of the tryparedoxin-tryparedoxin peroxidase couple unveil the structural determinants of Leishmania detoxification pathway. PLoS Neglected Tropical Disease 6, e1781.CrossRefGoogle ScholarPubMed
Frydman, J., Nimmesgern, E., Erdjument-Bromage, H., Wall, J. S., Tempst, P. and Hartl, F. U. (1992). Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits. EMBO Journal 11, 4767–4778.CrossRefGoogle ScholarPubMed
Gao, Y., Thomas, J. O., Chow, R. L., Lee, G. H. and Cowan, N. J. (1992). A cytoplasmic chaperonin that catalyzes beta-actin folding. Cell 69, 1043–1050.CrossRefGoogle ScholarPubMed
Gao, Y., Vainberg, I. E., Chow, R. L. and Cowan, N. J. (1993). Two cofactors and cytoplasmic chaperonin are required for the folding of alpha- and beta-tubulin. Molecular Cell Biology 13, 2478–2485.Google ScholarPubMed
Garg, R. and Dube, A. (2006). Animal models for vaccine studies for visceral leishmaniasis. Indian Journal of Medical Research 123, 439–454.Google ScholarPubMed
Garg, R., Gupta, S. K., Tripathi, P., Naik, S., Sundar, S. and Dube, A. (2005). Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani . Clinical and Experimental Immunology 140, 149–156.CrossRefGoogle ScholarPubMed
Garg, R., Gupta, S. K., Tripathi, P., Hajela, K., Sundar, S., Naik, S. and Dube, A. (2006). Leishmania donovani: identification of stimulatory soluble antigenic proteins using cured human and hamster lymphocytes for their prophylactic potential against visceral leishmaniasis. Vaccine 24, 2900–2909.CrossRefGoogle ScholarPubMed
Ghaffarifar, F., Jorjani, O., Sharifi, Z., Dalimi, A., Hassan, Z. M., Tabatabaie, F., Khoshzaban, F. and Hezarjaribi, H. Z. (2012). Enhancement of immune response induced by DNA vaccine cocktail expressing complete LACK and TSA genes against Leishmania major. APMIS 121, 290–298.CrossRefGoogle ScholarPubMed
Ghedin, E., Zhang, W. W., Charest, H., Sundar, S., Kenney, R. T. and Matlashewski, G. (1997). Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis. Clinical and Diagnostic Laboratory Immunology 4, 530–535.CrossRefGoogle ScholarPubMed
Ghose, A. C., Haldar, J. P., Pal, S. C., Mishra, B. P. and Mishra, K. K. (1980). Serological investigations on Indian kala-azar. Clinical and Experimental Immunology 40, 318–326.Google ScholarPubMed
Ghosh, A., Zhang, W. W. and Matlashewski, G. (2001). Immunization with A2 protein results in a mixed Th1/Th2 and a humoral response which protects mice against Leishmania donovani infections. Vaccine 20, 59–66.CrossRefGoogle Scholar
Gupta, S. K., Sisodia, B. S., Sinha, S., Hajela, K., Naik, S., Shasany, A. K. and Dube, A. (2007). Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes. Proteomics 7, 816–823.CrossRefGoogle ScholarPubMed
Gurunathan, S., Sacks, D. L., Brown, D. R., Reiner, S. L., Charest, H., Glaichenhaus, N. and Seder, R. A. (1997). Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major . Journal of Experimental Medicine 186, 1137–1147.CrossRefGoogle ScholarPubMed
Howard, J. G. and Liew, F. Y. (1984). Mechanisms of acquired immunity in leishmaniasis. Philosophical Transactions of the Royal Society London B Biological Science 307, 87–98.Google ScholarPubMed
Hsiao, C. H., Yao, C., Storlie, P., Donelson, J. E. and Wilson, M. E. (2008). The major surface protease (MSP or GP63) in the intracellular amastigote stage of Leishmania chagasi . Molecular and Biochemical Parasitology 157, 148–159.CrossRefGoogle ScholarPubMed
Iyer, J. P., Kaprakkaden, A., Choudhary, M. L. and Shaha, C. (2008). Crucial role of cytosolic tryparedoxin peroxidase in Leishmania donovani survival, drug response and virulence. Molecular Microbiology 68, 372–391.CrossRefGoogle ScholarPubMed
Jayakumar, A., Castilho, T. M., Park, E., Goldsmith-Pestana, K., Blackwell, J. M. and McMahon-Pratt, D. (2011). TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia). PLoS Neglected Tropical Disease 5, e1204.CrossRefGoogle ScholarPubMed
Kar, S., Soong, L., Colmenares, M., Goldsmith-Pestana, K. and McMahon-Pratt, D. (2000). The immunologically protective P-4 antigen of Leishmania amastigotes. A developmentally regulated single strand-specific nuclease associated with the endoplasmic reticulum. Journal of Biological Chemistry 275, 37789–37797.CrossRefGoogle ScholarPubMed
Khalil, E. A., El Hassan, A. M., Zijlstra, E. E., Mukhtar, M. M., Ghalib, H. W., Musa, B., Ibrahim, M. E., Kamil, A. A., Elsheikh, M., Babiker, A. and Modabber, F. (2000). Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan. Lancet 356, 1565–1569.CrossRefGoogle ScholarPubMed
Khare, P., Jaiswal, A. K., Tripathi, C. D., Joshi, S., Sundar, S. and Dube, A. (2013). Efficacy of Leishmania donovani trypanothione reductase, identified as a potent Th1 stimulatory protein, for its immunogenicity and prophylactic potential against experimental visceral leishmaniasis. Parasitology Research 113, 851–862.CrossRefGoogle ScholarPubMed
Kulkarni, M. M., Olson, C. L., Engman, D. M. and McGwire, B. S. (2009). Trypanosoma cruzi GP63 proteins undergo stage-specific differential posttranslational modification and are important for host cell infection. Infection and Immunity 77, 2193–2200.CrossRefGoogle ScholarPubMed
Kumari, S., Kumar, A., Samant, M., Sundar, S., Singh, N. and Dube, A. (2008 a). Proteomic approaches for discovery of new targets for vaccine and therapeutics against visceral leishmaniasis. Proteomics – Clinical Application, 3, 372–386.CrossRefGoogle Scholar
Kumari, S., Samant, M., Khare, P., Sundar, S., Sinha, S. and Dube, A. (2008 b). Induction of Th1-type cellular responses in cured/exposed Leishmania-infected patients and hamsters against polyproteins of soluble Leishmania donovani promastigotes ranging from 89·9 to 97·1 kDa. Vaccine 26, 4813–4818.CrossRefGoogle ScholarPubMed
Kumari, S., Samant, M., Misra, P., Khare, P., Sisodia, B., Shasany, A. K. and Dube, A. (2008 c). Th1-stimulatory polyproteins of soluble Leishmania donovani promastigotes ranging from 89·9 to 97·1 kDa offers long-lasting protection against experimental visceral leishmaniasis. Vaccine 26, 5700–5711.CrossRefGoogle ScholarPubMed
Kumari, S., Misra, P., Tandon, R., Samant, M., Sundar, S. and Dube, A. (2012). Leishmania donovani: immunostimulatory cellular responses of membrane and soluble protein fractions of splenic amastigotes in cured patient and hamsters. PLoS One 7, e30746.CrossRefGoogle ScholarPubMed
Kushawaha, P. K., Gupta, R., Tripathi, C. D., Khare, P., Jaiswal, A. K., Sundar, S. and Dube, A. (2012). Leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis. PLoS One 7, e45766.Google ScholarPubMed
Li, W. Z., Lin, P., Frydman, J., Boal, T. R., Cardillo, T. S., Richard, L. M., Toth, D., Lichtman, M. A., Hartl, F. U., Sherman, F. and Segel, G.B. (1994). Tcp20, a subunit of the eukaryotic TRiC chaperonin from humans and yeast. Journal of Biological Chemistry 269, 18616–18622.CrossRefGoogle ScholarPubMed
Liew, F. Y. (1991). Role of cytokines in killing of intracellular pathogens. Immunology Letters 30, 193–197.CrossRefGoogle ScholarPubMed
Liew, F. Y., Li, Y., Moss, D., Parkinson, C., Rogers, M. V. and Moncada, S. (1991). Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages. European Journal of Immunology 21, 3009–3014.CrossRefGoogle ScholarPubMed
Liew, F. Y., Millott, S., Parkinson, C., Palmer, R. M. and Moncada, S. (1990 a). Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. Journal of Immunology 144, 4794–4797.CrossRefGoogle ScholarPubMed
Liew, F. Y., Millott, S. M. and Schmidt, J. A. (1990 b). A repetitive peptide of Leishmania can activate T helper type 2 cells and enhance disease progression. Journal of Experimental Medicine 172, 1359–1365.CrossRefGoogle ScholarPubMed
Lin, Y. C., Hsu, J. Y., Chiang, S. C. and Lee, S. T. (2005). Distinct overexpression of cytosolic and mitochondrial tryparedoxin peroxidases results in preferential detoxification of different oxidants in arsenite-resistant Leishmania amazonensis with and without DNA amplification. Molecular Biochemistry and Parasitology 142, 66–75.CrossRefGoogle ScholarPubMed
MacMicking, J., Xie, Q. W. and Nathan, C. (1997). Nitric oxide and macrophage function. Annual Review of Immunology 15, 323–350.CrossRefGoogle ScholarPubMed
McMahon-Pratt, D., Kima, P. E. and Soong, L. (1998). Leishmania amastigote target antigens: the challenge of a stealthy intracellular parasite. Parasitology Today 14, 31–34.CrossRefGoogle ScholarPubMed
Melby, P. C., Tryon, V. V., Chandrasekar, B. and Freeman, G. L. (1998). Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of cytokine mRNA expression in experimental visceral leishmaniasis. Infection and Immunity 66, 2135–2142.CrossRefGoogle ScholarPubMed
Melby, P. C., Chandrasekar, B., Zhao, W. and Coe, J. E. (2001). The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response. Journal of Immunology 166, 1912–1920.CrossRefGoogle Scholar
Miklos, D., Caplan, S., Mertens, D., Hynes, G., Pitluk, Z., Kashi, Y., Harrison-Lavoie, K., Stevenson, S., Brown, C., and Barrell, B. (1994). Primary structure and function of a second essential member of the heterooligomeric TCP1 chaperonin complex of yeast, TCP1 beta. Proceedings of the National Academy of Sciences USA 91, 2743–2747.CrossRefGoogle ScholarPubMed
Misra, A., Dube, A., Srivastava, B., Sharma, P., Srivastava, J. K., Katiyar, J. C. and Naik, S. (2001). Successful vaccination against Leishmania donovani infection in Indian langur using alum-precipitated autoclaved Leishmania major with BCG. Vaccine 19, 3485–3492.CrossRefGoogle ScholarPubMed
Modabber, F. (1995). Vaccines against leishmaniasis. Annual of Tropical Medicine and Parasitology 89(Suppl. 1), 83–88.CrossRefGoogle ScholarPubMed
Murray, H. W., Montelibano, C., Peterson, R. and Sypek, J. P. (2000). Interleukin-12 regulates the response to chemotherapy in experimental visceral Leishmaniasis. Journal of Infectious Disease 182, 1497–1502.CrossRefGoogle ScholarPubMed
Nozaki, Y., Hasegawa, Y., Ichiyama, S., Nakashima, I. and Shimokata, K. (1997). Mechanism of nitric oxide-dependent killing of Mycobacterium bovis BCG in human alveolar macrophages. Infection and Immunity 65, 3644–3647.CrossRefGoogle ScholarPubMed
Nylen, S., Maasho, K., McMahon-Pratt, D. and Akuffo, H. (2004). Leishmanial amastigote antigen P-2 induces major histocompatibility complex class II-dependent natural killer-cell reactivity in cells from healthy donors. Scandinavian Journal of Immunology 59, 294–304.CrossRefGoogle ScholarPubMed
Osman, O. F., Kager, P. A. and Oskam, L. (2000). Leishmaniasis in the Sudan: a literature review with emphasis on clinical aspects. Tropical Medicine and International Health 5, 553–562.CrossRefGoogle Scholar
Pan, A. A. (1984). Leishmania mexicana: serial cultivation of intracellular stages in a cell-free medium. Experimental Parasitology 58, 72–80.CrossRefGoogle Scholar
Peruhype-Magalhaes, V., Martins-Filho, O. A., Prata, A., Silva Lde, A., Rabello, A., Teixeira-Carvalho, A., Figueiredo, R. M., Guimaraes-Carvalho, S. F., Ferrari, T. C. and Correa-Oliveira, R. (2005). Immune response in human visceral leishmaniasis: analysis of the correlation between innate immunity cytokine profile and disease outcome. Scandinavian Journal of Immunology 62, 487–495.CrossRefGoogle ScholarPubMed
Rafati, S., Baba, A. A., Bakhshayesh, M. and Vafa, M. (2000). Vaccination of BALB/c mice with Leishmania major amastigote-specific cysteine proteinase. Clinical and Experimental Immunology 120, 134–138.CrossRefGoogle ScholarPubMed
Rodríguez-Cortés, A., Ojeda, A., López-Fuertes, L., Timón, M., Altet, L., Solano-Gallego, L., Sánchez-Robert, E., Francino, O. and Alberola, J. (2007). Vaccination with plasmid DNA encoding KMPII, TRYP, LACK and GP63 does not protect dogs against Leishmania infantum experimental challenge. Vaccine 25, 7962–7971.CrossRefGoogle Scholar
Romao, S., Castro, H., Sousa, C., Carvalho, S. and Tomas, A. M. (2009). The cytosolic tryparedoxin of Leishmania infantum is essential for parasite survival. International Journal of Parasitology 39, 703–711.CrossRefGoogle ScholarPubMed
Samant, M., Gupta, R., Kumari, S., Misra, P., Khare, P., Kushawaha, P. K., Sahasrabuddhe, A. A. and Dube, A. (2009). Immunization with the DNA-encoding N-terminal domain of proteophosphoglycan of Leishmania donovani generates Th1-Type immunoprotective response against experimental visceral leishmaniasis. Journal of Immunology 183, 470–479.CrossRefGoogle ScholarPubMed
Scott, P., Pearce, E., Heath, S. and Sher, A. (1987). Identification of T-cell-reactive antigens that protect BALB/c mice against Leishmania major. Ann Inst Pasteur Immunol 138, 771–774.CrossRefGoogle ScholarPubMed
Singh, O. P., Stober, C. B., Singh, A. K., Blackwell, J. M. and Sundar, S. (2012). Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. PLoS Neglected Tropical Disese 6, e1874.Google Scholar
Sternlicht, H., Farr, G. W., Sternlicht, M. L., Driscoll, J. K., Willison, K. and Yaffe, M. B. (1993). The t-complex polypeptide 1 complex is a chaperonin for tubulin and actin in vivo. Proceedings of the National Academy of Science of the United States of America 90, 9422–9426.CrossRefGoogle ScholarPubMed
Stober, C. B., Lange, U. G., Roberts, M. T., Alcami, A. and Blackwell, J. M. (2005). IL-10 from regulatory T cells determines vaccine efficacy in murine Leishmania major infection. Journal of Immunology 175, 2517–2524.CrossRefGoogle ScholarPubMed
Stober, C. B., Lange, U. G., Roberts, M. T., Gilmartin, B., Francis, R., Almeida, R., Peacock, C. S., McCann, S. and Blackwell, J. M. (2006). From genome to vaccines for leishmaniasis: screening 100 novel vaccine candidates against murine Leishmania major infection. Vaccine 24, 2602–2616.CrossRefGoogle ScholarPubMed
Stober, C. B., Lange, U. G., Roberts, M. T., Alcami, A. and Blackwell, J. M. (2007). Heterologous priming-boosting with DNA and modified vaccinia virus Ankara expressing tryparedoxin peroxidase promotes long-term memory against Leishmania major in susceptible BALB/c Mice. Infection and Immunity 75, 852–860.CrossRefGoogle ScholarPubMed
Stober, C. B., Jeronimo, S. M., Pontes, N. N., Miller, E. N. and Blackwell, J. M. (2012). Cytokine responses to novel antigens in a peri-urban population in Brazil exposed to Leishmania infantum chagasi. The American Journal of Tropical Medical Hygiene 87, 663–670.CrossRefGoogle Scholar
Stoldt, V., Rademacher, F., Kehren, V., Ernst, J. F., Pearce, D. A. and Sherman, F. (1996). Review: the Cct eukaryotic chaperonin subunits of Saccharomyces cerevisiae and other yeasts. Yeast 12, 523–529.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Sundar, S. (2001). Drug resistance in Indian visceral leishmaniasis. Tropical Medicine and International Health 6, 849–854.CrossRefGoogle ScholarPubMed
Sundar, S. and Rai, M. (2005). Treatment of visceral leishmaniasis. Expert Opinion on Pharmacotherapy 6, 2821–2829.CrossRefGoogle ScholarPubMed
Sundar, S., Reed, S. G., Sharma, S., Mehrotra, A. and Murray, H. W. (1997). Circulating T helper 1 (Th1) cell- and Th2 cell-associated cytokines in Indian patients with visceral leishmaniasis. The American Journal of Tropical Medicine and Hygiene 56, 522–525.CrossRefGoogle ScholarPubMed
Sundar, S., Pai, K., Kumar, R., Pathak-Tripathi, K., Gam, A. A., Ray, M. and Kenney, R. T. (2001). Resistance to treatment in Kala-azar: speciation of isolates from northeast India. The American Journal of Tropical Medicine and Hygiene 65, 193–196.CrossRefGoogle ScholarPubMed
Todoli, F., Solano-Gallego, L., de Juan, R., Morell, P., Nunez Mdel, C., Lasa, R., Gomez-Sebastian, S., Escribano, J. M., Alberola, J. and Rodriguez-Cortes, A. (2010). Humoral and in vivo cellular immunity against the raw insect-derived recombinant Leishmania infantum antigens KMPII, TRYP, LACK, and papLe22 in dogs from an endemic area. The American Journal of Tropical Medicine and Hygiene 83, 1287–1294.CrossRefGoogle ScholarPubMed
Towbin, H., Staehelin, T. and Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of National Academy of Sciences of the United States of America 76, 4350–4354.CrossRefGoogle ScholarPubMed
Vieira, L. Q., Goldschmidt, M., Nashleanas, M., Pfeffer, K., Mak, T. and Scott, P. (1996). Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection with Leishmania major, but control parasite replication. Journal of Immunology 157, 827–835.CrossRefGoogle ScholarPubMed
Walker, J., Acestor, N., Gongora, R., Quadroni, M., Segura, I., Fasel, N. and Saravia, N. G. (2006). Comparative protein profiling identifies elongation factor-1beta and tryparedoxin peroxidase as factors associated with metastasis in Leishmania guyanensis . Molecular Biochemical and Parasitology 145, 254–264.CrossRefGoogle ScholarPubMed
Warren, H. S., Vogel, F. R. and Chedid, L. A. (1986). Current status of immunological adjuvants. Annual Review of Immunology 4, 369–388.CrossRefGoogle ScholarPubMed
Webb, J. R., Kaufmann, D., Campos-Neto, A. and Reed, S. G. (1996). Molecular cloning of a novel protein antigen of Leishmania major that elicits a potent immune response in experimental murine leishmaniasis. Journal of Immunology 157, 5034–5041.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Wilkinson, S. R., Horn, D., Prathalingam, S. R. and Kelly, J. M. (2003). RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the African trypanosome. Journal of Biological Chemistry 278, 31640–31646.CrossRefGoogle Scholar
Yaffe, M. B., Farr, G. W., Miklos, D., Horwich, A. L., Sternlicht, M. L. and Sternlicht, H. (1992). TCP1 complex is a molecular chaperone in tubulin biogenesis. Nature 358, 245–248.CrossRefGoogle ScholarPubMed
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 ScholarPubMed
Zanin, F. H., Coelho, E. A., Tavares, C. A., Marques-da-Silva, E. A., Silva Costa, M. M., Rezende, S. A., Gazzinelli, R. T. and Fernandes, A. P. (2007). Evaluation of immune responses and protection induced by A2 and nucleoside hydrolase (NH) DNA vaccines against Leishmania chagasi and Leishmania amazonensis experimental infections. Microbes and Infection 9, 1070–1077.CrossRefGoogle ScholarPubMed