title: SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.
abstract: Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India.
authors.forename: Junaid Jibran
authors.initials: JJ
authors.lastname: Jawed
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India.
authors.forename: Syamdas
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India.
authors.forename: Satabdi
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India.
authors.forename: Shabina
authors.initials: S
authors.lastname: Parveen
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata-700054, India subrata@bic.boseinst.ernet.in.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000276:immunology*; D064546:Protein Kinase C beta / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D018836:Inflammation Mediators; D054332:Leishmaniasis Vaccines; D010457:Peptidoglycan; D064546:Protein Kinase C beta
keywords: Leishmania donovani; PGN; PKCβ; SLA; Th17