Skip Navigation LinksHome > March 13, 2013 - Volume 27 - Issue 5 > Dendritic cell-specific intercellular adhesion molecule-3 gr...
AIDS:
doi: 10.1097/QAD.0b013e32835cfc82
Basic Science

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

Cassol, Edanaa,b,c; Cassetta, Lucaa,b; Rizzi, Chiaraa; Gabuzda, Danac; Alfano, Massimoa,*; Poli, Guidoa,b,*

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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 CD4+ T lymphocytes.

Methods: MDM were incubated with either tumour necrosis factor-alpha (TNF-α) along with interferon-gamma (IFN-γ) or with interleukin-4 (IL-4) for 18 h to obtain M1 or M2a cells, respectively. Expression of cell surface antigens, including CD4 and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), 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 from MDM to IL-2 activated CD4+ 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 CD4 cell expression. M2a-MDM efficiently transmitted both R5 and X4 HIV-1 to CD4+ T cells in a DC-SIGN-dependent manner.

Conclusion: DC-SIGN facilitates HIV-1 infection of M2a-MDM, and HIV-1 transfer from M2a-MDM to CD4+ T cells. M2a-polarized tissue macrophages may play an important role in the capture and spread of HIV-1 in mucosal tissues and placenta.

© 2013 Lippincott Williams & Wilkins, Inc.

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