Leishmania-Specific Promiscuous Membrane Protein Tubulin Folding Cofactor D Divulges Th1/Th2 Polarization in the Host via ERK-1/2 and p38 MAPK Signaling Cascade
Autor: | Manish K Singh, Sanjiva Bimal, Mohd Saad Umar, Anzar Abdul Mujeeb, Swaleha Zubair, Ghufran Ahmad, Shubhankar K. Singh, Manas Ranjan Dikhit, Pushpanjali, Pradeep Das, Fauzia Jamal, Mohammad Owais, Jagadish Hansa |
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Rok vydání: | 2020 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine MAPK/ERK pathway In silico Immunology Leishmania donovani MAPK signaling Biology tubulin folding cofactor D 03 medical and health sciences 0302 clinical medicine Immune system peptide cocktail medicine Immunology and Allergy Original Research T-cell proliferation immunoprophylaxis biology.organism_classification medicine.disease Leishmania Isotype Cell biology 030104 developmental biology Visceral leishmaniasis Th1 response biology.protein Antibody lcsh:RC581-607 humoral response 030217 neurology & neurosurgery |
Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
ISSN: | 1664-3224 |
DOI: | 10.3389/fimmu.2020.00817 |
Popis: | 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. |
Databáze: | OpenAIRE |
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