Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.
Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.
Bray
Mike
M
Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mbray@niaid.nih.gov
Geisbert
Thomas W
TW
D000818:Animals; D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology*; D029043:Ebolavirus / Q000472:pathogenicity*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D011323:Primates