Human cytomegalovirus inhibits cytokine-induced macrophage differentiation.
Human cytomegalovirus (HCMV) infection in immunocompromised patients is associated with impaired immunological function. Blood monocytes, which differentiate into macrophage effector cells, are of central importance for immune reactivity. Here, we demonstrate that HCMV transiently blocks cytokine-induced differentiation of monocytes into functionally active phagocytic macrophages. In HCMV-treated cultures, the cells had classical macrophage markers but lacked the classical morphological appearance of macrophages and had impairments in migration and phagocytosis. Even at very low multiplicities of infection, macrophage differentiation was almost completely inhibited. The inhibition appeared to be mediated by a soluble factor released upon viral treatment of monocytes. Human immunodeficiency virus or measles virus had no such effects. These findings suggest that HCMV impairs immune function by blocking certain aspects of cytokine-induced differentiation of monocytes and demonstrate an efficient pathway for this virus to evade immune recognition that may have clinical implications for the generalized immunosuppression often observed in HCMV-infected patients.
Gredmark
Sara
S
Karolinska Systems Biomedicine Center, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
Tilburgs
Tamara
T
Söderberg-Nauclér
Cecilia
C
D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003587:Cytomegalovirus / Q000472:pathogenicity*; D006678:HIV / Q000472:pathogenicity; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D008459:Measles virus / Q000472:pathogenicity; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology / Q000821:virology*; D010587:Phagocytosis
D015415:Biomarkers; D016207:Cytokines; D016898:Interferon-alpha; D015850:Interleukin-6; D016753:Interleukin-10; D007371:Interferon-gamma