title: Natural killer cell-mediated response to human cytomegalovirus-infected macrophages is modulated by their functional polarization.
abstract: MΦ comprise a heterogeneous population of cells, which contribute to host defense and maintenance of immune homeostasis. MΦ may be infected by human cytomegalovirus (HCMV), which has evolved different strategies to subvert the immune response. In the present study, we comparatively analyzed the natural killer (NK) cell response against HCMV (TB40E)-infected proinflammatory (M1) and antinflammatory (M2) MΦ, derived from autologous monocytes, cultured in the presence of GM-CSF and M-CSF, respectively. M1 MΦ were more resistant to infection and secreted IL-6, TNF-α, IFN-α, and IL-12; by contrast, in HCMV-infected M2 MΦ, proinflammatory cytokines, IL-10, and IFN-α production were limited and IL-12 was undetectable. NK cell degranulation was triggered by interaction with HCMV-infected M1 and M2 MΦ at 48 h postinfection. The response was partially inhibited by specific anti-NKp46, anti-DNAM-1, and anti-2B4 mAb, thus supporting a dominant role of these activating receptors. By contrast, only HCMV-infected M1 MΦ efficiently promoted NK cell-mediated IFN-γ secretion, an effect partially related to IL-12 production. These observations reveal differences in the NK cell response triggered by distinct, HCMV-infected, monocyte-derived cell types, which may be relevant in the immunopathology of this viral infection.
authors: Immunology Unit, Pompeu Fabra University, Barcelona, Spain.
authors: Neus
authors: N
authors: Romo
authors: Giuliana
authors: G
authors: Magri
authors: Aura
authors: A
authors: Muntasell
authors: Gemma
authors: G
authors: Heredia
authors: Diogo
authors: D
authors: Baía
authors: Ana
authors: A
authors: Angulo
authors: Monica
authors: M
authors: Guma
authors: Miguel
authors: M
authors: López-Botet
mesh_terms: D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D015846:Monokines / Q000276:immunology*; D013997:Time Factors
chemical_list: D015846:Monokines