Gene profiling analysis of ALVAC infected human monocyte derived dendritic cells
Autor: | Franca Spada, Anke Harenberg, Elizabeth J. Ryan, Florine Guillaume, Nicolas Burdin |
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Rok vydání: | 2008 |
Předmět: |
Immunoblotting
Gene Expression HIV Infections HIV Envelope Protein gp120 Microarray Biology Canarypox virus Monocytes Article Immune system Interferon medicine Humans Ubiquitins Innate immunity ALVAC Innate immune system General Veterinary General Immunology and Microbiology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Monocyte Public Health Environmental and Occupational Health Viral Vaccines Dendritic Cells Dendritic cell Virology HIV Envelope Protein gp41 Chemokine CXCL10 IRF Infectious Diseases medicine.anatomical_structure Type I interferon signaling pathway Interferon Type I Immunology HIV-1 Cytokines RNA Molecular Medicine IRF7 IRF3 medicine.drug |
Zdroj: | Vaccine |
ISSN: | 0264-410X |
DOI: | 10.1016/j.vaccine.2008.07.050 |
Popis: | The recombinant canarypox virus ALVAC is being extensively studied as vaccine vector for the development of new vaccine strategies against chronic infectious diseases and cancer. However, the mechanisms by which ALVAC initiates the immune response have not been completely elucidated. In order to determine the type of innate immunity triggered by ALVAC, we characterized the gene expression profile of human monocyte derived dendritic cells (MDDCs) upon ALVAC infection. These cells are permissive to poxvirus infection and play a key role in the initiation of immune responses. The majority of the genes that were up-regulated by ALVAC belong to the type I interferon signaling pathway including IRF7, STAT1, RIG-1, and MDA-5. Genes involved in the NF-kappaB pathway were not up-regulated. The gene encoding for the chemokine CXCL10, a direct target of the transcription factor IRF3 was among those up-regulated and DC secretion of CXCL10 following exposure to ALVAC was confirmed by ELISA. Many downstream type I interferon activated genes with anti-viral activity (PKR, Mx, ISG15 and OAS among others) were also up-regulated in response to ALVAC. Among these, ISG15 expression in its unconjugated form by Western blot analysis was demonstrated. In view of these results we propose that ALVAC induces type I interferon anti-viral innate immunity via a cytosolic pattern-recognition-receptor (PRR) sensing double-stranded DNA, through activation of IRF3 and IRF7. These findings may aid in the design of more effective ALVAC-vectored vaccines. |
Databáze: | OpenAIRE |
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