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

Autor: Beatriz C.S. Salles, Vívian T. Martins, Lourena E. Costa, Marcelo P Oliveira, Daniel Dias, Ricardo Andrez Machado-de-Ávila, Antônio Lúcio Teixeira, Patrícia A.F. Ribeiro, Daniela P. Lage, Mônica Santos Schneider, Miguel A. Chávez-Fumagalli, Thaís T.O. Santos, Eduardo A.F. Coelho, Fernanda F. Ramos
Rok vydání: 2018
Předmět:
0301 basic medicine
Protozoan Proteins
Epitopes
T-Lymphocyte
Parasite load
immune response
Virulence factor
0302 clinical medicine
Interferon
vaccine
visceral leishmaniasis
Leishmania infantum
Spectroscopy
Leishmania
Infectivity
Immunity
Cellular
Mice
Inbred BALB C
biology
bioinformatics
General Medicine
peripheral blood mononuclear cells
Computer Science Applications
small myristoylated protein-3
Cytokines
Leishmaniasis
Visceral
medicine.drug
Virulence Factors
030231 tropical medicine
Virulence
Antigens
Protozoan
Article
Catalysis
Microbiology
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Humans
Amino Acid Sequence
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
Computational Biology
Reproducibility of Results
Molecular Sequence Annotation
Leishmaniasis
biology.organism_classification
medicine.disease
Immunity
Humoral
030104 developmental biology
Visceral leishmaniasis
Structural Homology
Protein
Leukocytes
Mononuclear
Linear Models
Zdroj: International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 129
International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: 10.3390/ijms19010129
Popis: 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.
Databáze: OpenAIRE
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