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Int. J. Mol. Sci. 2018, 19(1), 129; doi:10.3390/ijms19010129

Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis

1
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
2
Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma 88806-000, Santa Catarina, Brazil
3
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
4
Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Road, Houston, TX 77041, USA
5
Departamento de Patologia Clínica, do Colégio Técnico (COLTEC), Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil
*
Author to whom correspondence should be addressed.
Received: 2 November 2017 / Revised: 14 December 2017 / Accepted: 25 December 2017 / Published: 3 January 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

In a proteomics approach conducted with Leishmania amazonensis, parasite proteins showed either an increase or a decrease in their expression content during extensive in vitro cultivation, and were related to the survival and the infectivity of the parasites, respectively. In the current study, a computational screening was performed to predict virulence factors among these molecules. Three proteins were selected, one of which presented no homology to human proteins. This candidate, namely small myristoylated protein-3 (SMP-3), was cloned, and its recombinant version (rSMP-3) was used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy subjects living in an endemic area of leishmaniasis and from visceral leishmaniasis patients. Results showed high interferon-γ (IFN-γ) production and low levels of interleukin 10 (IL-10) in the cell supernatants. An in vivo experiment was then conducted on BALB/c mice, which were immunized with rSMP-3/saponin and later challenged with Leishmania infantum promastigotes. The rSMP-3/saponin combination induced high production of protein-specific IFN-γ, IL-12, and granulocyte-macrophage colony-stimulating factor (GM-CSF) by the spleen cells of the immunized mice. This pattern was associated with protection, which was characterized by a significant reduction in the parasite load in distinct organs of the animals. Altogether, these results have revealed that this new virulence factor is immunogenic in both mice and humans, and have proven its protective efficacy against visceral leishmaniasis in a murine model. View Full-Text
Keywords: visceral leishmaniasis; bioinformatics; small myristoylated protein-3; peripheral blood mononuclear cells; immune response; vaccine visceral leishmaniasis; bioinformatics; small myristoylated protein-3; peripheral blood mononuclear cells; immune response; vaccine
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MDPI and ACS Style

Oliveira, M.P.; Martins, V.T.; Santos, T.T.O.; Lage, D.P.; Ramos, F.F.; Salles, B.C.S.; Costa, L.E.; Dias, D.S.; Ribeiro, P.A.F.; Schneider, M.S.; Machado-de-Ávila, R.A.; Teixeira, A.L.; Coelho, E.A.F.; Chávez-Fumagalli, M.A. Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis. Int. J. Mol. Sci. 2018, 19, 129.

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