AUTHOR=Jamal Fauzia , Singh Manish K. , Hansa Jagadish , Pushpanjali  , Ahmad Ghufran , Dikhit Manas Ranjan , Umar Mohd Saad , Bimal Sanjiva , Das Pradeep , Mujeeb Anzar Abdul , Singh Shubhankar K. , Zubair Swaleha , Owais Mohammad 

TITLE=RETRACTED: 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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00817

DOI=10.3389/fimmu.2020.00817

ISSN=1664-3224

ABSTRACT=<p>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. <italic>In silico</italic> analysis of <italic>Leishmania</italic> tubulin folding cofactor D protein predicted its potential to activate both B- and T-cell repertoires. Furthermore, the ELISA employing anti-peptide<sub>27</sub> (a segment of tubulin folding cofactor D) antibody revealed its proficiency in VL diagnosis and treatment monitoring. The peptide<sub>27</sub> and its cocktail with another <italic>Leishmania</italic> peptide (peptide<sub>23</sub>) prompted the up-regulation of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-2, IL-17, <italic>etc</italic>., 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, <italic>etc</italic>. We also established that the peptide cocktail modulated host MAPK signaling to favor the amplification of Th<sub>1</sub>-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 <italic>Leishmania donovani</italic>.</p>