Τίτλος:
Induction of protective cellular immune responses against experimental visceral leishmaniasis mediated by dendritic cells pulsed with the N-terminal domain of Leishmania infantum elongation factor-2 and CpG oligodeoxynucleotides
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Leishmania elongation factor 2 (EF-2) has been previously identified as a T H 1-stimulatory protein. In this study, we assayed the protective potential of the N-terminal domain of EF-2 (N-LiEF-2, 1–357 aa) that has been predicted to contain several overlapping MHC class I and II-restricted epitopes injected in the form of dendritic cell (DC)-based vaccine. Ex vivo pulsing of DCs with the recombinant N-LiEF-2 domain along with CpG oligodeoxynucleotides (ODNs) resulted in their functional differentiation. BALB/c vaccinated with CpG-triggered DCs pulsed with N-LiEF-2 were found to be the most immune-reactive in terms of induction of DTH responses, increased T cell proliferation and IL-2 production. Moreover, vaccination induced antigen-specific T H 1 type immune response as evidenced by increased IFN-γ and TNFα levels followed by a significant increase of nitrite (NO) and reactive oxygen species (ROS) in splenocyte cultures. Vaccinated mice showed a pronounced decrease in parasite load in spleen and liver when challenged with L. infantum, increased expression of Stat1 and Tbx21 mRNA transcripts versus reduced expression of Foxp3 transcripts and were able to produce significantly elevated levels of IL-2, IFN-γ and TNFα but not IL-10 compared to non-vaccinated mice. Both antigen and parasite-specific CD4 + T and CD8 + T cells contributed to the IFN-γ production indicating that both subtypes contribute to the resistance to infection and correlated with robust nitrite generation, critical in controlling Leishmania infection. Together, these findings demonstrated the immunogenic as well as protective potential of the N-terminal domain of Leishmania EF-2 when given with CpG-triggered DCs representing a basis for the development of rationalized vaccine against leishmaniasis. © 2018 Elsevier Ltd
Συγγραφείς:
Agallou, M.
Pantazi, E.
Tsiftsaki, E.
Toubanaki, D.K.
Gaitanaki, C.
Smirlis, D.
Karagouni, E.
Περιοδικό:
Cellular and Molecular Immunology
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
CD4 antigen; CD8 antigen; CpG oligodeoxynucleotide; dendritic cell vaccine; elongation factor 2; gamma interferon; interleukin 10; interleukin 2; major histocompatibility antigen class 1; major histocompatibility antigen class 2; messenger RNA; nitrite; reactive oxygen metabolite; STAT1 protein; transcription factor FOXP3; transcription factor T bet; tumor necrosis factor; CPG-oligonucleotide; elongation factor 2; gamma interferon; Leishmania vaccine; oligodeoxyribonucleotide; parasite antigen; protective agent; protozoal protein, amino acid sequence; amino terminal sequence; animal cell; animal experiment; animal model; antigen presenting cell; antigen specificity; Article; CD4+ T lymphocyte; CD8+ T lymphocyte; cellular immunity; controlled study; cytokine production; dendritic cell; experimental visceral leishmaniasis; female; humoral immunity; immunogenicity; interferon production; Leishmania infantum; lymphocyte proliferation; mouse; nonhuman; parasite load; priority journal; protein domain; protein expression; spleen cell; Th1 cell; vaccination; animal; Bagg albino mouse; cell culture; cellular immunity; chemistry; dendritic cell; drug effect; immunology; Leishmania donovani; Leishmania infantum; metabolism; parasitology; physiology; T lymphocyte; visceral leishmaniasis, Animals; Antigens, Protozoan; Cells, Cultured; Dendritic Cells; Female; Immunity, Cellular; Interferon-gamma; Leishmania donovani; Leishmania infantum; Leishmaniasis Vaccines; Leishmaniasis, Visceral; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Peptide Elongation Factor 2; Protective Agents; Protozoan Proteins; T-Lymphocytes
DOI:
10.1016/j.molimm.2018.08.004
