Journal
AIDS
Volume 27, Issue 5, Pages 707-716Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e32835cfc82
Keywords
dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin; HIV transmission; HIV-1; macrophage polarization; T cells
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Funding
- Fondation Dormeur
- Europrise [LSHP CT-2006-037611]
- Italian Ministry of Health Grant Program of AIDS Research
- CIHR fellowship
- NIH [R01 MH83588]
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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-alpha) along with interferon-gamma (IFN-gamma) 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. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:707-716
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