title: Modulation of the immune and inflammatory responses by Plasmodium falciparum schizont extracts: role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes.
abstract: The optimal immune response to malaria infection comprises rapid induction of inflammatory responses promptly counteracted by regulatory mechanisms to prevent immunopathology. To evaluate the role of dendritic cells (DC) in the balance of parasite-induced inflammatory/anti-inflammatory mechanisms, we studied the activity of monocyte-derived dendritic cells (MDDC), previously exposed to soluble extracts of Plasmodium falciparum-infected red blood cells (PfSE), in the differentiation of CD4 cells isolated from donors never exposed to malaria infection. We show that MDDC exposed to PfSE are extremely efficient to induce a contemporary differentiation of TH1 effector cells and T regulatory (Treg) cells in CD4 T cells even when exposed to low concentrations of parasitic extracts. Treg cells induced by MDDC infected with PfSE (MDDC-PfSE) produce transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) and are endowed with strong suppressive properties. They also show phenotypical and functional peculiarities, such as the contemporary expression of markers of Treg and TH1 differentiation and higher sensitivity to TLR4 ligands both inducing an increasing production of suppressive cytokines. On the whole, our data indicate that MDDC exposed to PfSE orchestrate a well-balanced immune response with timely differentiation of TH1 and Treg cells in CD4 cells from nonimmune donors and suggest that, during the infection, the role of MDCC could be particularly relevant in low-parasitemia conditions.
authors.affiliation: Department of Clinical Physiopathology, University of Florence, Italy.
authors.forename: Ann Maria
authors.initials: AM
authors.lastname: Clemente
authors.forename: Giulia
authors.initials: G
authors.lastname: Fadigati
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporale
authors.forename: Damiano G
authors.initials: DG
authors.lastname: Marchese
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castronovo
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Sannella
authors.forename: Carlo
authors.initials: C
authors.lastname: Severini
authors.forename: Federica
authors.initials: F
authors.lastname: Verra
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Federico
authors.initials: F
authors.lastname: Cozzolino
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Torcia
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*
chemical_list: D016207:Cytokines