Dengue-2 infection and the induction of apoptosis in human primary monocytes.
Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-alpha and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
Amanda
A
Torrentes-Carvalho
Elzinandes L
EL
Azeredo
Sonia R I
SR
Reis
Alessandro S
AS
Miranda
Mariana
M
Gandini
Luciana S
LS
Barbosa
Claire F
CF
Kubelka
D017209:Apoptosis / Q000276:immunology*; D003715:Dengue / Q000276:immunology / Q000821:virology*; D003716:Dengue Virus / Q000145:classification / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D010718:Phosphatidylserines / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D010718:Phosphatidylserines; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D016753:Interleukin-10