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.
aAIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute
bVita-Salute San Raffaele University, School of Medicine, Milan, Italy
cDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
*Massimo Alfano and Guido Poli equally contributed to the writing of this article.
Correspondence to Dr Edana Cassol, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. E-mail: firstname.lastname@example.org
Received 16 March, 2010
Revised 5 November, 2012
Accepted 23 November, 2012