title: HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype.
abstract: Numerical and functional defects in plasmacytoid dendritic cells (pDCs) are an important hallmark of progressive HIV-1 infection, yet its etiology remains obscure. HIV-1 p17 matrix protein (p17) modulates a variety of cellular responses, and its biological activity depends on the expression of p17 receptors (p17Rs) on the surface of target cells. In this study, we show that peripheral blood pDCs express p17Rs on their surface and that freshly isolated pDCs are sensitive to p17 stimulation. Upon p17 treatment, pDCs undergo phenotypic differentiation with up-regulation of CCR7. A chemotaxis assay reveals that p17-treated pDCs migrate in response to CCL19, suggesting that these cells may acquire the ability to migrate to secondary lymphoid organs. In contrast, p17 does not induce release of type I IFN nor does it enhance pDC expression of CD80, CD86, CD83, or MHC class II. Microarray gene expression analysis indicated that p17-stimulated pDCs down-regulate the expression of molecules whose functions are crucial for efficient protein synthesis, protection from apoptosis, and cell proliferation induction. Based on these results, we propose a model where p17 induces immature circulating pDCs to home in lymph nodes devoid of their ability to serve as a link between innate and adaptative immune systems.
authors.affiliation: Sections of Microbiology, General Pathology and Immunology, and Pathology, University of Brescia, I-25123 Brescia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fiorentini
authors.forename: Elena
authors.initials: E
authors.lastname: Riboldi
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Manuela
authors.initials: M
authors.lastname: Avolio
authors.forename: Marco
authors.initials: M
authors.lastname: Fabbri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tosti
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Becker
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054415:Chemokine CCL19; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D015488:HIV Antigens / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D015658:HIV Infections / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000494:pharmacology
chemical_list: D054415:Chemokine CCL19; D015488:HIV Antigens; D016898:Interferon-alpha; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1