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. 2000 Jan;74(1):556-9.
doi: 10.1128/jvi.74.1.556-559.2000.

Measles virus induces functional TRAIL production by human dendritic cells

P O Vidalain  1 , O Azocar, B Lamouille, A Astier, C Rabourdin-Combe, C Servet-Delprat
Affiliations

Measles virus induces functional TRAIL production by human dendritic cells

P O Vidalain et al. J Virol. 2000 Jan.

Abstract

Measles virus infection induces a profound immunosuppression that can lead to serious secondary infections. Here we demonstrate that measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression in human monocyte-derived dendritic cells. Moreover, measles virus-infected dendritic cells are shown to be cytotoxic via the TRAIL pathway.

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Figures

FIG. 1
FIG. 1
Analysis of TRAIL and FasL mRNA expression in MV-infected or mock-treated DCs. TRAIL and FasL mRNA expression was quantified by performing an RNase protection assay (Riboquant hApo3) on total RNA extracts in accordance with the manufacturer's (PharMingen) specifications. (A) DCs were either mock treated (Mock-DCs) or infected with MV at 1 PFU/cell (MV-DCs), then cultured for 0, 4, 8, 12, or 24 h. (B) DCs were either mock treated or infected with MV at 0.01, 0.1, or 1 PFU/cell as described above, then placed in culture and harvested 24 h later. For both panels, L32 mRNA, encoding a constitutively expressed ribosomal protein, was used as a control probe. Data shown are representative of three experiments; standard deviations were always below 10%.
FIG. 2
FIG. 2
Determination of TRAIL expression in MV-infected or mock-treated DCs or monocytes by flow cytometry and Western blot analysis. DCs and monocytes were either mock treated or infected with MV at 1 PFU/cell, then placed in culture for 24 h. (A and B) DCs (A) and monocytes (B) were stained with an anti-TRAIL antibody after mock treatment (open histograms) or MV infection (gray histograms). Dotted histograms represent staining with an isotypic control. (C) Similar staining was also performed after permeabilization of DCs infected with 0.1 PFU/cell. (D) TRAIL expression in uninfected (DCs) or MV-infected (MV-DCs) DCs cultured for 12, 24, or 36 h was analyzed by Western blotting. Protein extracts were separated by SDS–10% PAGE, transferred to a membrane, and blotted with either a specific monoclonal anti-TRAIL antibody or an anti-β-tubulin antibody (as a protein loading control). The positions of molecular mass markers are shown on the right. Data shown are representative of three experiments; standard deviations were always below 10%.
FIG. 3
FIG. 3
Role of TRAIL in the cytotoxic activity of MV-infected DCs and monocytes. DCs and monocytes were either mock treated (Mock-DCs and Mock-Mono, respectively) or MV infected (MV-DCs and MV-Mono, respectively), then placed in culture for 12 h. Harvested monocytes (A) and DCs (B) were then cultured with 51Cr-labeled MDA-231 target cells at the indicated effector-to-target cell (E/T) ratios. TRAIL-R2:Fc or TNF-R1:Fc chimeras (20 μg/ml) were added or not added to the assay to inhibit TRAIL or TNF-α-induced cell death. 51Cr release was measured 8 h later. Results are means of data from three experiments; in all cases, standard deviations were below 8%.
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