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Elongation factor-2, a Th1 stimulatory protein of Leishmania donovani, generates strong IFN-γ and IL-12 response in cured Leishmania-infected patients/hamsters and protects hamsters against Leishmania challenge

Kushawaha, Pramod K ; Gupta, Reema ; Sundar, Shyam ; Sahasrabuddhe, Amogh A ; Dube, Anuradha

The Journal of immunology (1950), 2011-12, Vol.187 (12), p.6417-6427 [Periódico revisado por pares]

United States

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Elongation factor-2, a Th1 stimulatory protein of Leishmania donovani, generates strong IFN-γ and IL-12 response in cured Leishmania-infected patients/hamsters and protects hamsters against Leishmania challenge
Autor: Kushawaha, Pramod K ; Gupta, Reema ; Sundar, Shyam ; Sahasrabuddhe, Amogh A ; Dube, Anuradha
Assuntos: Adolescent ; Adult ; Animals ; Cell Line ; Cell Proliferation ; Child ; Child, Preschool ; Clonal Selection, Antigen-Mediated - immunology ; Cricetinae ; Disease Models, Animal ; Female ; Humans ; Interferon-gamma - biosynthesis ; Interleukin-12 - biosynthesis ; Leishmania donovani ; Leishmania donovani - immunology ; Leishmaniasis Vaccines - administration & dosage ; Leishmaniasis Vaccines - genetics ; Leishmaniasis Vaccines - immunology ; Leishmaniasis, Visceral - immunology ; Leishmaniasis, Visceral - pathology ; Leishmaniasis, Visceral - prevention & control ; Male ; Mesocricetus ; Mesocricetus auratus ; Mice ; Middle Aged ; Molecular Sequence Data ; Protozoan Proteins - physiology ; Th1 Cells - immunology ; Th1 Cells - parasitology ; Th1 Cells - pathology
É parte de: The Journal of immunology (1950), 2011-12, Vol.187 (12), p.6417-6427
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Descrição: In visceral leishmaniasis, Th1 types of immune responses correlate with recovery from and resistance to disease, and resolution of infection results in lifelong immunity against the disease. Leishmanial Ags that elicit proliferative and cytokine responses in PBMCs from cured/exposed/Leishmania patients have been characterized through proteomic approaches, and elongation factor-2 is identified as one of the potent immunostimulatory proteins. In this study, we report the cloning and expression of Leishmania donovani elongation factor-2 protein (LelF-2) and its immunogenicity in PBMCs of cured/exposed Leishmania-infected patients and hamsters (Mesocricetus auratus). Leishmania-infected cured/exposed patients and hamsters exhibited significantly higher proliferative responses to recombinant Lelf-2 (rLelF-2) than those with L. donovani-infected hosts. The soluble L. donovani Ag stimulated PBMCs of cured/exposed and Leishmania patients to produce a mixed Thl/Th2-type cytokine profile, whereas rLelF-2 stimulated the production of IFN-γ, IL-12, and TNF-α but not IL-4 or IL-10. Further, rLelF-2 downregulated LPS-induced IL-10 as well as soluble L. donovani Ag-induced IL-4 production by Leishmania patient PBMCs. The immunogenicity of rLelF-2 was also checked in hamsters in which rLelF-2 generates strong IL-12- and IFN-γ-mediated Th1 immune response. This was further supported by a remarkable increase in IgG2 Ab level. We further demonstrated that rLelF-2 was able to provide considerable protection (∼65%) to hamsters against L. donovani challenge. The efficacy was supported by the increased inducible NO synthase mRNA transcript and Th1-type cytokines IFN-γ, IL-12, and TNF-α and downregulation of IL-4, IL-10, and TGF-β. Hence, it is inferred that rLelF-2 elicits a Th1 type of immune response exclusively and confers considerable protection against experimental visceral leishmaniasis.
Editor: United States
Idioma: Inglês

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Elongation factor-2, a Th1 stimulatory protein of Leishmania donovani, generates strong IFN-γ and IL-12 response in cured Leishmania-infected patients/hamsters and protects hamsters against Leishmania challenge

Kushawaha, Pramod K ; Gupta, Reema ; Sundar, Shyam ; Sahasrabuddhe, Amogh A ; Dube, Anuradha

United States

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