title: CSP--a model for in vivo presentation of Plasmodium berghei sporozoite antigens by hepatocytes.
abstract: One target of protective immunity against the Plasmodium liver stage in BALB/c mice is represented by the circumsporozoite protein (CSP), and mainly involves its recognition by IFN-γ producing specific CD8+T-cells. In a previous in vitro study we showed that primary hepatocytes from BALB/c mice process Plasmodium berghei (Pb) CSP (PbCSP) and present CSP-derived peptides to specific H-2k(d) restricted CD8+T-cells with subsequent killing of the presenting cells. We now extend these observations to an in vivo infection model in which infected hepatocytes and antigen specific T-cell clones are transferred into recipient mice inducing protection from sporozoite (SPZ) challenge. In addition, using a similar protocol, we suggest the capacity of hepatocytes in priming of naïve T-cells to provide protection, as further confirmed by induction of protection after depletion of cross-presenting dendritic cells (DCs) by cytochrome c (cyt c) treatment or using traversal deficient parasites. Our results clearly show that hepatocytes present Plasmodium CSP to specific-primed CD8+T-cells, and could also prime naïve T-cells, leading to protection from infection. These results could contribute to a better understanding of liver stage immune response and design of malaria vaccines.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Saidou
authors.initials: S
authors.lastname: Balam
authors.forename: Jackeline F
authors.initials: JF
authors.lastname: Romero
authors.forename: Silayuv E
authors.initials: SE
authors.lastname: Bongfen
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045304:Cytochromes c / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D034101:Sporozoites / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D045304:Cytochromes c