Monocyte-derived human macrophages and peripheral blood mononuclear cells infected with ebola virus secrete MIP-1alpha and TNF-alpha and inhibit poly-IC-induced IFN-alpha in vitro.
Ebola virus infection of humans is associated with high levels of circulating inflammatory chemokines and cytokines. We demonstrate that direct infection of human PBMC results in the induction of MCP-1, MIP-1alpha, RANTES, and TNF-alpha as early as 24 h p.i. in response to live virus. Monocyte-derived macrophages infected with live Ebola-virus secreted MIP-1alpha and TNF-alpha specifically while RANTES and MCP-1 were secreted by with both live or inactivated virus stimulation and do not require viral replication. Type I interferons (IFN-alpha and -beta), IL-1beta and IL-10, were not induced by Ebola virus. Furthermore, live virus infection of both PBMCs and monocytes-derived macrophages inhibited IFN-alpha induced by double-stranded RNA in vitro. These data provide the first direct evidence of a role for macrophages in the pathogenesis to Ebola virus and suggest that Ebola virus can inhibit cellular antiviral mechanisms mediated by type I interferons.
Gupta
M
M
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Mahanty
S
S
Ahmed
R
R
Rollin
P E
PE
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D029043:Ebolavirus; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D016899:Interferon-beta / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016898:Interferon-alpha; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016899:Interferon-beta; D011070:Poly I-C