title: Immunostimulatory properties of the Leishmania infantum heat shock proteins HSP70 and HSP83.
abstract: Emerging evidence indicates that the heat shock proteins (HSPs), a set of highly evolutionary conserved proteins, are playing essential roles in both normal processes of the immune system and specific immune responses. In a previous work, we demonstrated that the Leishmania infantum HSP70 possesses remarkable immunostimulatory properties. In the present work, we have extended the study to another HSP from this parasite, the HSP83. We show that this protein also has an adjuvant effect to an accompanying protein by stimulation of the humoral response when both proteins are fused and co-administered to BALBjc mice. The analysis of the IgG isotypes, IgG1 and IgG2a, indicated that the immunisations with the Leishmania HSPs, mainly the HSP70, potentiate a Thl-type response. It was found that the amino-terminal domain of the HSP70, the most evolutionary conserved region of the molecule, maintains the ability to stimulate the humoral response, whereas the carboxyl-terminal domain does not have a similar effect. Unexpectedly, we found that the L. infantum HSP70 and HSP83 recombinant proteins stimulated the proliferation of spleen cells from unprimed BALB/c mice. Remarkably, this proliferation was abolished either by thermal denaturing of the proteins or by using specific antibodies. The use of the T-cell inhibitor cyclosporin A in the splenocytes proliferation assays suggested that both T- and non-T-cells are stimulated by the Leishmania HSPs. These findings may be relevant for therapeutic and prophylactic applications.
authors.affiliation: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Rico
authors.forename: S O
authors.initials: SO
authors.lastname: Angel
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: J M
authors.initials: JM
authors.lastname: Requena
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D016572:Cyclosporine / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D007114:Immunization; D066298:In Vitro Techniques; D018314:Leishmania infantum / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C490310:Hsp83 protein, protozoan; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine