Protection against filarial infection by 45-49kDa molecules ofBrugia malayivia IFN-[gamma]-mediated iNOS induction

Nitric oxide (NO) mediated mechanisms have been implicated in killing of some life-stages ofBrugia malayi/Wuchereria bancroftiand protect the host through type 1 responses and IFN-γ stimulated toxic mediators' release. However, the identity of NO stimulating molecules of the parasites is not kn...

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Bibliographic Details
Published in:Vaccine 2015-01, Vol.33 (4), p.527
Main Authors: Verma, Shiv K, Joseph, Sujith K, Verma, Richa, Kushwaha, Vikas, Parmar, Naveen, Yadav, Pawan K, Thota, Jagadeshwar Reddy, Kar, Susanta, Murthy, P Kalpana
Format: Article
Language:English
Subjects:
Antigens
Confidence intervals
Cytokines
Experiments
Immunization
Immunology
Infections
Laboratory animals
Nitric oxide
Parasites
Peptides
Proteins
Rodents
Studies
Tropical diseases
Worms
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Summary:Nitric oxide (NO) mediated mechanisms have been implicated in killing of some life-stages ofBrugia malayi/Wuchereria bancroftiand protect the host through type 1 responses and IFN-γ stimulated toxic mediators' release. However, the identity of NO stimulating molecules of the parasites is not known. Three predominantly NO-stimulating SDS-PAGE resolved fractions F8 (45.24-48.64kDa), F11 (33.44-38.44kDa) and F12 (28.44-33.44kDa) fromB. malayiwere identified and their proteins were analyzed by 2-DE and MALDI-TOF/TOF. Tropomyosin, calponin and de novo peptides were identified by 2-DE and MALDI-TOF/TOF in F8 and immunization with F8 conferred most significant protection against L3-initiated infection inMastomys coucha. Immunized animals showed upregulated F8-induced NO, IFN-γ, TNF-, IL-1β, IL-10, TGF-β release, cellular proliferative responses and specific IgG and IgG1. Anti-IFN-γ, anti-TNF-, and anti-IL-1β significantly reduced F8-mediated NO generation and iNOS induction at protein levels. Anti-IFN-γ treated cells showed maximum reduction (>74%) in NO generation suggesting a predominant role of IFN-γ in iNOS induction. In conclusion, the findings suggest that F8 which contains tropomyosin, calponin and de novo peptides protects the host via IFN-γ mediated iNOS induction and may hold promise as vaccine candidate(s). This is also the first report of identification of tropomyosin and calponin inB. malayi.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2014.11.041