HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype
| Autor: | Giorgio Tosti, Carlos A. Guzmán, Marco Fabbri, Elena Riboldi, Silvano Sozzani, Arnaldo Caruso, Fabio Facchetti, Simona Fiorentini, Manuela Avolio, Pablo D. Becker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Receptors
CCR7 HIV Antigens viruses Cellular differentiation HIV Infections Receptors Cell Surface C-C chemokine receptor type 7 Biology gag Gene Products Human Immunodeficiency Virus Cell Movement immune system diseases Humans CD86 Regulation of gene expression MHC class II Multidisciplinary Tumor Necrosis Factor-alpha Chemotaxis CCL19 Interferon-alpha virus diseases Cell Differentiation hemic and immune systems Dendritic Cells Biological Sciences Flow Cytometry Immunohistochemistry Cell biology Phenotype Gene Expression Regulation biology.protein Chemokine CCL19 Lymph Nodes CD80 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|