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
Authors: Manas Ranjan Dikhit
Mohammad Owais
Swaleha Zubair
Pradeep Das
Manish K Singh
Pushpanjali
Mohd Saad Umar
Fauzia Jamal
Jagadish Hansa
Ghufran Ahmad
Shubhankar K Singh
Anzar Abdul Mujeeb
Sanjiva Bimal
Journal: Frontiers in Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: Leishmania donovani; MAPK signaling; T-cell proliferation; Th1 response; humoral response
Affiliations: Interdesciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India., Department of Microbiology, Rajendra Memorial Research Institute of Medical Sciences, Patna, India., Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna, India., Department of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna, India., Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Patna, India., Department of Computer Science, Aligarh Muslim University, Aligarh, India.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. In Figure 9, several panels look similar to each other. Pointed out with red and blue boxes. Some additional points appear to be visible in the bottom right Day 63 panel not visible in the other panels marked in red. ![file] , 
 September 2020 correction.  In the original article, there was a error in Figure 9C as published. The flow panels were inadvertently misarranged. The corrected Figure 9 appears below. (...) The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Could the authors please clarify how at least three panels were mis-arranged, and how the gated percentages of those panels were different while the plots were identical? In addition, the new, corrected, Figure 9C raises new concerns. * While some plots have been replaced by other plots, the gated percentages are still the same as in the original figure. * The new top  Unvaccinated panel looks very similar to the new bottom  Cocktail vaccinated (day 30) panel, as marked by me below with cyan rounded boxes. The similarities are not perfect, though, as the Unvaccinated panel appears to contain dots not present in the  Cocktail plat, shown with blue circles. * The new  Cocktail vaccinated (day 30) panel on the top row looks somewhat similar to the new  Unvaccinated panel on the bottom row. Shown with orange rounded boxes. ![file] , 
 June 2021 Retraction, found here: https: www.frontiersin.org articles 10.3389 fimmu.2021.724474 full It reads:  The journal and Chief Editors retracts the 02 June 2020 article cited above. Following the publication of the original article, image duplication concerns in the published article were identified in Figure 9. There were instances where multiple panels within the figure were duplicated. Upon issuing a Correction article, further issues were identified within the figure panels, namely similarities in the dot patterns between flow cytometry plots. The authors were unable to provide a satisfactory explanation for these occurrences and could not provide the original flow cytometry data. As a result, the data and conclusions of the article may be unreliable. The article and the Correction are therefore being retracted. This retraction was approved by the Specialty and Field Chief Editors of Frontiers in Immunology and the Editor-in-Chief of Frontiers. The authors did not agree to this retraction. ,