Protection against filarial infection by 45–49 kDa molecules of Brugia malayi via IFN-γ-mediated iNOS induction |
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| Institution: | 1. Department of Epidemiology, IRCCS — Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy;2. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy;1. Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Avenida Instituto Politécnico Nacional # 2508, Colonia San Pedro Zacatenco, Delegación Gustavo A. Madero, C.P. 07360, México, D.F., México;2. Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, Avenida 19 Poniente esquina 4a Norte s/n, Colonia Centro, C.P. 62100 Tapachula, Chiapas, Mexico;3. Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA;4. Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad # 655, Colonia Santa María Ahuacatitlán, C.P. 62100, Cuernavaca, Morelos, México;5. Departments of Molecular Biology and Biochemistry, and Microbiology and Molecular Genetics, University of California, Irvine, CA 92697, USA |
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| Abstract: | Nitric oxide (NO) mediated mechanisms have been implicated in killing of some life-stages of Brugia malayi/Wuchereria bancrofti and 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 (45.24–48.64 kDa), F11 (33.44–38.44 kDa) and F12 (28.44–33.44 kDa) from B. malayi were 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 in Mastomys coucha. Immunized animals showed upregulated F8-induced NO, IFN-γ, TNF-α, IL-1β, IL-10, TGF-β release, cellular proliferative responses and specific IgG and IgG1. Anti-IFN-γ, anti-TNF-α, 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 in B. malayi. |
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| Keywords: | NO stimulating molecules iNOS Cytokines 2-DE MALDI-MS IgG and its subclasses LTT assay |
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