title: Mannoproteins from Cryptococcus neoformans promote dendritic cell maturation and activation.
abstract: Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IkappaBalpha phosphorylation, which is necessary for nuclear factor kappaB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietrella
authors.forename: Cristina
authors.initials: C
authors.lastname: Corbucci
authors.forename: Stefano
authors.initials: S
authors.lastname: Perito
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bistoni
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000954:Antigens, Surface / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C025363:mannoproteins