Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.
Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.
Mahanty
Siddhartha
S
Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. smahanty@cdc.gov
Hutchinson
Karen
K
Agarwal
Sudhanshu
S
McRae
Michael
M
Rollin
Pierre E
PE
Pulendran
Bali
B
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D029043:Ebolavirus / Q000276:immunology* / Q000472:pathogenicity; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000821:virology; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D007835:Lassa Fever / Q000276:immunology / Q000821:virology; D007836:Lassa virus / Q000276:immunology* / Q000472:pathogenicity; D009000:Monocytes / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology