title: Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin mediates HIV-1 infection of and transmission by M2a-polarized macrophages in vitro.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. edana_cassol@dfci.harvard.edu
authors.forename: Edana
authors.initials: E
authors.lastname: Cassol
authors.forename: Luca
authors.initials: L
authors.lastname: Cassetta
authors.forename: Chiara
authors.initials: C
authors.lastname: Rizzi
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
authors.forename: Massimo
authors.initials: M
authors.lastname: Alfano
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005434:Flow Cytometry; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D015999:Multivariate Analysis; D019713:Receptors, CCR5 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin