Abstract
BackgroundAppropriate induction of the early Th1 cytokine IL-12 is a critical defense directed against viral infection. We have previously shown that different viruses elicited either IL-12 or IFNα dependent Th1 reactions. Using dengue-2 virus, we sought to explore how dengue-2 induced IL-12 or IFNα expression by monocytic and its derived dendritic cells.MethodsWe employed human monocytic cell line, THP-1, to investigate whether differentiation of monocytic cells is involved in the switch between IFNα and IL-12 induction. Flow cytometry, RT-PCR and ELISA were respectively used to determine cell differentiation, IL-12 and IFNα mRNA expression and protein production.ResultsTHP-1, expressing CD123, which is a plasmacytoid dendritic cell marker, but not CD14, CD11b or CD11c revealed IFNα mRNA expression while stimulated by dengue-2. In contrast, PMA-induced THP-1 differentiation toward monocytic cells expressed CD11b+, and CD14+, but not CD123, and revealed exclusively IL-12 expression while stimulated by dengue-2. Further studies showed that CD123+ expressing THP-1 cells elicited higher IFNα expression in dose and time dependent induction after infection, and PMA-induced monocytic differentiation of THP-1 cells revealed IL-12 expression. Antibody-dependent enhancement of DEN-2 infection significantly suppressed the DEN-2 induced IL-12 p40 expression in monocytic differentiated THP-1 cells.ConclusionsClarification and modulation of the early Th1 reaction in different monocytic cells may change or prevent complication from dengue infection.
Highlights
Appropriate induction of the early Th1 cytokine IL-12 is a critical defense directed against viral infection
Undifferentiated THP-1 expressing pDC markers released IFNα but not IL-12 after dengue viruses (DEN)-2 infection In order to characterize the expression of cell markers on THP-1 cells, we assessed the CD123 levels, a pDCspecific marker, on THP-1 cells by flow cytometry
Higher levels of IFNα mRNA but not IL12B mRNA were induced in post-infected THP-1 cells by DEN-2 (Figure 1B)
Summary
Appropriate induction of the early Th1 cytokine IL-12 is a critical defense directed against viral infection. Dengue fever (DF) is transmitted by mosquitoe bite which introduces dengue viruses (DEN) including 4 serotypes. Occasional, DF progresses to dengue hemorrhagic fever (DHF), a potentially life threatening complication associated with vascular leakage, hemorrhage, thrombocytopenia and shock [3,4,5]. More than 1 billion people are at risk of dengue infection and there are approximately 100 million cases of DF and 500,000 cases of DHF every year [6]. DHF has been classified into four could induce IL-12 or IFNα to polarize Th1 reaction in a mutually exclusive fashion [16]. Different viruses induce IL-12 or IFNα mutually exclusive is usually mediated via ligation of different toll-like receptors (TLRs) [19,20,21]
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