Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin mediates HIV-1 infection of and transmission by M2a-polarized macrophages in vitro

Edana Cassol, Luca Cassetta, Chiara Rizzi, Dana Gabuzda, Massimo Alfano, Guido Poli

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To assess in-vitro effects of monocyte-derived macrophage (MDM) polarization into M1 and M2a cells on HIV-1 replication and transmission and obtain new insights into the potential importance of macrophage polarization in vivo. Design: Human peripheral blood monocytes were differentiated into MDM for 7 days. Control and MDM polarized into M1 or M2a cells were exposed to different strains of HIV-1 and assessed for their ability to bind and transmit virus to CD+ T lymphocytes. Methods: MDM were incubated with either tumour necrosis factor-alpha (TNF-a) along with interferon-gamma (IFN-g) or with interleukin-4 (IL-4) for 18 h to obtain M1 or M2a cells, respectively. Expression of cell surface antigens, including CD+ and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DCSIGN), was evaluated by flow cytometry. C-C chemokine receptor type 5 (CCR5)- dependent (R5) HIV-1 binding, DNA synthesis and viral replication were assessed in the presence or absence of anti-DC-SIGN blocking mAbs. Transmission of C-X-C chemokine receptor type 4 (CXCR4)-dependent (X4) and R5 HIV-1 fromMDMto IL-2 activated CD+ T cells was also investigated. Results: DC-SIGN was strongly upregulated on M2a-MDM and downregulated on M1- MDM compared with control MDM. DC-SIGN facilitated HIV-1 entry and DNA synthesis in M2a-MDM, compensating for their low levels of CD+ cell expression. M2a-MDM efficiently transmitted both R5 and X4 HIV-1 to CD+ T cells in a DC-SIGNdependent manner. Conclusion: DC-SIGN facilitates HIV-1 infection of M2a-MDM, and HIV-1 transfer from M2a-MDM to CD+ T cells. M2a-polarized tissue macrophages may play an important role in the capture and spread of HIV-1 in mucosal tissues and placenta.

Original languageEnglish
Pages (from-to)707-716
Number of pages10
JournalAIDS (London, England)
Volume27
Issue number5
DOIs
Publication statusPublished - Mar 13 2013

Keywords

  • Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin
  • HIV transmission
  • HIV-1
  • Macrophage polarization
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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