Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-11T22:44:09.078Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunological characterization of a chimeric form of Schistosoma mansoni aquaporin in the murine model

Published online by Cambridge University Press:  01 May 2014

BARBARA CASTRO PIMENTEL FIGUEIREDO ,
NATAN RAIMUNDO GONÇALVES DE ASSIS ,
SUELLEN BATISTONI DE MORAIS ,
VICENTE PAULO MARTINS Open the ORCID record for VICENTE PAULO MARTINS [Opens in a new window] ,
NATASHA DELAQUA RICCI ,
RODRIGO MARQUES BICALHO ,
CARINA DA SILVA PINHEIRO  and
SERGIO COSTA OLIVEIRA
BARBARA CASTRO PIMENTEL FIGUEIREDO
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
NATAN RAIMUNDO GONÇALVES DE ASSIS
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
SUELLEN BATISTONI DE MORAIS
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
VICENTE PAULO MARTINS
Affiliation:
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil Departamento de Biologia Celular do Instituto de Ciências Biológicas, Universidade de Brasília, 70910-900 Brasília, DF, Brazil
NATASHA DELAQUA RICCI
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
RODRIGO MARQUES BICALHO
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
CARINA DA SILVA PINHEIRO
Affiliation:
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil Departamento de Biointeração do Instituto de Ciências da Saúde, Universidade Federal da Bahia, 40110-100, Salvador, BA, Brazil
SERGIO COSTA OLIVEIRA*
Affiliation:
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, MG, Brazil
*
*Corresponding author: Av. Antônio Carlos, 6627 – Pampulha – Caixa Postal 486, Belo Horizonte, MG, Brazil31270-901. E-mail: scozeus1@gmail.com
Get access Rights & Permissions [Opens in a new window]

Summary

Aquaporin (SmAQP) is the most abundant transmembrane protein in the tegument of Schistosoma mansoni. This protein is expressed in all developmental stages and seems to be essential in parasite survival since it plays a crucial role in osmoregulation, nutrient transport and drug uptake. In this study, we utilized the murine model to evaluate whether this protein was able to induce protection against challenge infection with S. mansoni cercariae. A chimeric (c) SmAQP was formulated with Freund's adjuvant for vaccination trial and evaluation of the host's immune response was performed. Our results demonstrated that immunization with cSmAQP induced the production of high levels of specific anti-cSmAQP IgG antibodies and a Th1/Th17 type of immune response characterized by IFN-γ, TNF-α and IL-17 cytokines. However, vaccination of mice with cSmAQP failed to reduce S. mansoni worm burden and liver pathology. Finally, we were unable to detect humoral immune response anti-cSmAQP in the sera of S. mansoni-infected human patients. Our results lead us to believe that SmAQP, as formulated in this study, may not be a good target in the search for an anti-schistosomiasis vaccine.

Keywords

Schistosoma mansonitegumentaquaporinvaccineTh1/Th17 response
Type
Research Article
Information
Parasitology , Volume 141 , Issue 10 , September 2014 , pp. 1277 - 1288
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

Amiri, P., Locksley, R. M., Parslow, T. G., Sadick, M., Rector, E., Ritter, D. and McKerrow, J. H. (1992). Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature 356, 604–607. doi: 10.1038/356604a0.Google Scholar
Bazzone, L. E., Smith, P. M., Rutitzky, L. I., Shainheit, M. G., Urban, J. F., Setiawan, T., Blum, A. M., Weinstock, J. V. and Stadecker, M. J. (2008). Coinfection with the intestinal nematode Heligmosomoides polygyrus markedly reduces hepatic egg-induced immunopathology and proinflammatory cytokines in mouse models of severe schistosomiasis. Infection and Immunity 76, 5164–5172. doi: 10.1128/IAI.00673-08.CrossRefGoogle ScholarPubMed
Bergquist, N. R., Leonardo, L. R. and Mitchell, G. F. (2005). Vaccine-linked chemotherapy: can schistosomiasis control benefit from an integrated approach? Trends in Parasitology 21, 112–117. doi: 10.1016/j.pt.2005.01.001.Google Scholar
Braschi, S. and Wilson, R. A. (2006). Proteins exposed at the adult schistosome surface revealed by biotinylation. Molecular and Cellular Proteomics 5, 347–356. doi: 10.1074/mcp.M500287-MCP200.Google Scholar
Braschi, S., Curwen, R. S., Ashton, P. D., Verjovski-Almeida, S. and Wilson, A. (2006). The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction. Proteomics 6, 1471–1482. doi: 10.1002/pmic.200500368.Google Scholar
Brito, C. F., Fonseca, C. T., Goes, A. M., Azevedo, V., Simpson, A. J. and Oliveira, S. C. (2000). Human IgG1 and IgG3 recognition of Schistosoma mansoni 14 kDa fatty acid-binding recombinant protein. Parasite Immunology 22, 41–48.Google Scholar
Capron, A., Bazin, H., Dessaint, J. P. and Capron, M. (1975). The role of specific IgE antibodies in the immune adherence of normal macrophages to schistosomes of Schistosoma mansoni . Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences D: Sciences Naturelles 280, 927–930.Google ScholarPubMed
Cardoso, F. C., Pacifico, R. N., Mortara, R. A. and Oliveira, S. C. (2006). Human antibody responses of patients living in endemic areas for schistosomiasis to the tegumental protein Sm29 identified through genomic studies. Clinical and Experimental Immunology (Oxford) 144, 382–391. doi: 10.1111/j.1365-2249.2006.03081.x.CrossRefGoogle Scholar
Cardoso, L. S., Araujo, M. I., Goes, A. M., Pacifico, L. G., Oliveira, R. R. and Oliveira, S. C. (2007). Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis. Microbial Cell Factories 6, 1. doi: 10.1186/1475-2859-6-1.Google Scholar
Cardoso, F. C., Macedo, G. C., Gava, E., Kitten, G. T., Mati, V. L., de Melo, A. L., Caliari, M. V., Almeida, G. T., Venancio, T. M., Verjovski-Almeida, S. and Oliveira, S. C. (2008). Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection. PLoS Neglected Tropical Diseases 2, e308. doi: 10.1371/journal.pntd.0000308.Google Scholar
Castro-Borges, W., Simpson, D. M., Dowle, A., Curwen, R. S., Thomas-Oates, J., Beynon, R. J. and Wilson, R. A. (2011). Abundance of tegument surface proteins in the human blood fluke Schistosoma mansoni determined by QconCAT proteomics. Journal of Proteomics 74, 1519–1533. doi: 10.1016/j.jprot.2011.06.011.CrossRefGoogle ScholarPubMed
Cheever, A. W., Poindexter, R. W. and Wynn, T. A. (1999). Egg laying is delayed but worm fecundity is normal in SCID mice infected with Schistosoma japonicum and S. mansoni with or without recombinant tumor necrosis factor alpha treatment. Infection and Immunity 67, 2201–2208.CrossRefGoogle ScholarPubMed
Delgado, V. and McLaren, D. J. (1990). Evidence for enhancement of IgG1 subclass expression in mice polyvaccinated with radiation-attenuated cercariae of Schistosoma mansoni and the role of this isotype in serum-transferred immunity. Parasite Immunology 12, 15–32.Google Scholar
Faghiri, Z. and Skelly, P. J. (2009). The role of tegumental aquaporin from the human parasitic worm, Schistosoma mansoni, in osmoregulation and drug uptake. FASEB Journal 23, 2780–2789. doi: 10.1096/fj.09-130757.Google Scholar
Faghiri, Z., Camargo, S. M., Huggel, K., Forster, I. C., Ndegwa, D., Verrey, F. and Skelly, P. J. (2010). The tegument of the human parasitic worm Schistosoma mansoni as an excretory organ: the surface aquaporin SmAQP is a lactate transporter. PLoS One 5, e10451. doi: 10.1371/journal.pone.0010451.Google Scholar
Fonseca, C. T., Brito, C. F., Alves, J. B. and Oliveira, S. C. (2004). IL-12 enhances protective immunity in mice engendered by immunization with recombinant 14 kDa Schistosoma mansoni fatty acid-binding protein through an IFN-gamma and TNF-alpha dependent pathway. Vaccine 22, 503–510.Google Scholar
Fonseca, C. T., Pacifico, L. G., Barsante, M. M., Rassi, T., Cassali, G. D. and Oliveira, S. C. (2006). Co-administration of plasmid expressing IL-12 with 14-kDa Schistosoma mansoni fatty acid-binding protein cDNA alters immune response profiles and fails to enhance protection induced by Sm14 DNA vaccine alone. Microbes and Infection 8, 2509–2516. doi: 10.1016/j.micinf.2006.06.008.CrossRefGoogle ScholarPubMed
Gonen, T. and Walz, T. (2006). The structure of aquaporins. Quarterly Reviews of Biophysics 39, 361–396. doi: 10.1017/S0033583506004458.Google Scholar
Gray, D. J., McManus, D. P., Li, Y., Williams, G. M., Bergquist, R. and Ross, A. G. (2010). Schistosomiasis elimination: lessons from the past guide the future. Lancet Infectious Diseases 10, 733–736. doi: 10.1016/S1473-3099(10)70099-2.Google Scholar
Jankovic, D., Wynn, T. A., Kullberg, M. C., Hieny, S., Caspar, P., James, S., Cheever, A. W. and Sher, A. (1999). Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanisms. Journal of Immunology 162, 345–351.Google Scholar
Khalife, J., Dunne, D. W., Richardson, B. A., Mazza, G., Thorne, K. J., Capron, A. and Butterworth, A. E. (1989). Functional role of human IgG subclasses in eosinophil-mediated killing of schistosomula of Schistosoma mansoni . Journal of Immunology 142, 4422–4427.Google Scholar
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.Google Scholar
Loukas, A., Tran, M. and Pearson, M. S. (2007). Schistosome membrane proteins as vaccines. International Journal for Parasitology 37, 257–263. doi: 10.1016/j.ijpara.2006.12.001.Google Scholar
Lustigman, S., Prichard, R. K., Gazzinelli, A., Grant, W. N., Boatin, B. A., McCarthy, J. S. and Basanez, M. G. (2012). A research agenda for helminth diseases of humans: the problem of helminthiases. PLoS Neglected Tropical Diseases 6, e1582. doi: 10.1371/journal.pntd.0001582.Google Scholar
McManus, D. P. (2012). Schistosomiasis in 2012: current status and key research priorities required for control leading to elimination. Expert Review of Anti-infective Therapy 10, 1233–1236. doi: 10.1586/eri.12.121.CrossRefGoogle ScholarPubMed
McManus, D. P. and Loukas, A. (2008). Current status of vaccines for schistosomiasis. Clinical Microbiology Reviews 21, 225–242. doi: 10.1128/CMR.00046-07.Google Scholar
Medzhitov, R. (2007). Recognition of microorganisms and activation of the immune response. Nature 449, 819–826. doi: 10.1038/nature06246.Google Scholar
Pacifico, L. G., Fonseca, C. T., Chiari, L. and Oliveira, S. C. (2006). Immunization with Schistosoma mansoni 22·6 kDa antigen induces partial protection against experimental infection in a recombinant protein form but not as DNA vaccine. Immunobiology 211, 97–104. doi: 10.1016/j.imbio.2005.06.004.Google Scholar
Pearce, E. J. and MacDonald, A. S. (2002). The immunobiology of schistosomiasis. Nature Reviews Immunology 2, 499–511. doi: 10.1038/nri843.Google Scholar
Pearson, M. S., Pickering, D. A., McSorley, H. J., Bethony, J. M., Tribolet, L., Dougall, A. M., Hotez, P. J. and Loukas, A. (2012). Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. PLOS Neglected Tropical Diseases 6, e1564. doi: 10.1371/journal.pntd.0001564.Google Scholar
Pinheiro, C. S., Martins, V. P., Assis, N. R., Figueiredo, B. C., Morais, S. B., Azevedo, V. and Oliveira, S. C. (2011). Computational vaccinology: an important strategy to discover new potential S. mansoni vaccine candidates. Journal of Biomedicine and Biotechnology 2011, 503068. doi: 10.1155/2011/503068.Google Scholar
Prichard, R. K., Basanez, M. G., Boatin, B. A., McCarthy, J. S., Garcia, H. H., Yang, G. J., Sripa, B. and Lustigman, S. (2012). A research agenda for helminth diseases of humans: intervention for control and elimination. PLOS Neglected Tropical Diseases 6, e1549. doi: 10.1371/journal.pntd.0001549.Google Scholar
Romeih, M. H., Hassan, H. M., Shousha, T. S. and Saber, M. A. (2008). Immunization against Egyptian Schistosoma mansoni infection by multivalent DNA vaccine. Acta Biochimica et Biophysica Sinica (Shanghai) 40, 327–338.Google Scholar
Rutitzky, L. I. and Stadecker, M. J. (2011). Exacerbated egg-induced immunopathology in murine Schistosoma mansoni infection is primarily mediated by IL-17 and restrained by IFN-gamma. European Journal of Immunology 41, 2677–2687. doi: 10.1002/eji.201041327.Google Scholar
Steinmann, P., Keiser, J., Bos, R., Tanner, M. and Utzinger, J. (2006). Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infectious Diseases 6, 411–425. doi: 10.1016/S1473-3099(06)70521-7.Google Scholar
Towbin, H., Staehelin, T. and Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences USA 76, 4350–4354.Google Scholar
Tran, M. H., Pearson, M. S., Bethony, J. M., Smyth, D. J., Jones, M. K., Duke, M., Don, T. A., McManus, D. P., Correa-Oliveira, R. and Loukas, A. (2006). Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nature Medicine 12, 835–840. doi: 10.1038/nm1430.Google Scholar
van der Werf, M. J., de Vlas, S. J., Brooker, S., Looman, C. W., Nagelkerke, N. J., Habbema, J. D. and Engels, D. (2003). Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Tropica 86, 125–139.Google Scholar
Wilson, R. A., Coulson, P. S., Betts, C., Dowling, M. A. and Smythies, L. E. (1996). Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology 87, 275–282.Google Scholar
World Health Organization (2010). Working to Overcome the Global Impact of Neglected Tropical Diseases. First WHO Report on Neglected Tropical Diseases. World Health Organization, Geneva, Switzerland.Google Scholar
Supplementary material: File

Figueiredo Supplementary Material

Supplementary Material

Download Figueiredo Supplementary Material(File)
File 20.8 KB