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Front Immunol ; 11: 817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582140

RESUMO

Visceral leishmaniasis (VL)-related mortality and morbidity imposes a great deal of health concern across the globe. The existing anti-leishmanial drug regimen generally fails to eliminate newly emerging resistant isolates of this dreadful parasite. In such circumstances, the development of a prophylactic strategy to impart protection against the disease is likely to take center stage. In order to develop a promising prophylactic vaccine, it is desirable to identify an adequately potential vaccine candidate. In silico analysis of Leishmania tubulin folding cofactor D protein predicted its potential to activate both B- and T-cell repertoires. Furthermore, the ELISA employing anti-peptide27 (a segment of tubulin folding cofactor D) antibody revealed its proficiency in VL diagnosis and treatment monitoring. The peptide27 and its cocktail with another Leishmania peptide (peptide23) prompted the up-regulation of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-2, IL-17, etc., and the down-regulation of immune-regulatory cytokines, such as IL-10, in the immunized BALB/c mice. Coherent to the consequence of peptide-specific humoral immune response, peptide cocktail-based immunization ensued in the predominant amplification of pathogen-specific IgG2a over the IgG1 isotype, up-regulated proliferation of T lymphocytes, and enhanced production of nitric oxide, reactive oxygen species, etc. We also established that the peptide cocktail modulated host MAPK signaling to favor the amplification of Th1-dominated immune response in the host. The peptide cocktail mediated the activation of the host immune armory, which was eventually translated into a significant decline in parasitic load in the visceral organs of experimental animals challenged with Leishmania donovani.


Assuntos
Polaridade Celular/imunologia , Leishmania donovani/imunologia , Leishmaniose Visceral/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Proteínas Associadas aos Microtúbulos/imunologia , Proteínas de Protozoários/imunologia , Células Th1/imunologia , Células Th2/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Adulto Jovem
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