HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype

Simona Fiorentini, Elena Riboldi, Fabio Facchetti, Manuela Avolio, Marco Fabbri, Giorgio Tosti, Pablo D. Becker, Carlos A. Guzman, Silvano Sozzani, Arnaldo Caruso

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3867-3872
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number10
DOIs
Publication statusPublished - Mar 25 2008

Keywords

  • CCR7 chemokine receptor
  • Immune deregulation

ASJC Scopus subject areas

  • Genetics
  • General

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