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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cassatella, Marco A. Grisendi, Giulia De Gironcoli, Marzia Bussmeyer, Uta Calzetti, Federica Masala, Caterina Musso, Tiziana Le Moigne, Vincent Scutera, Sara Costantini, Claudio Bazzoni, Flavia Tamassia, Nicola |
| Description | Country affiliation: Italy Author Affiliation: Tamassia N ( Section of General Pathology, Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy.) |
| Abstract | Upon LPS binding, TLR4 activates a MyD88-dependent pathway leading to the transcriptional activation of proinflammatory genes, as well as a MyD88-independent/TRIF-dependent pathway, responsible for the transcriptional induction of IFN-ß. Previous findings delineated that human neutrophils are unable to induce the transcription of IFN-ß in response to TLR4 stimulation. Because neutrophils do not express protein kinase C ε, a molecule recently reported as essential for initiating the MyD88-independent/TRIF-dependent pathway, we optimized an electroporation method to transfect PKCε into neutrophils with very high efficiency. By doing so, a significant IFN-ß mRNA expression was induced, in the absence of LPS stimulation, not only in PKCε-overexpressing neutrophils but also in cells transfected with a series of empty DNA plasmids; however, LPS further upregulated the IFN-ß transcript levels in plasmid-transfected neutrophils, regardless of PKCε overexpression. Phosphoimmunoblotting studies, as well as chromatin immunoprecipitation assays targeting the IFN-ß promoter, revealed that IFN-ß mRNA induction occurred through the cooperative action of IRF3, activated by transfected DNA, and NF-κB, activated by LPS. Additional immunoblotting and coimmunoprecipitation studies revealed that neutrophils constitutively express various cytosolic DNA sensors, including IFN-inducible protein 16, leucine-rich repeat (in Flightless I) interacting protein-1, and DDX41, as well as that IFN-inducible protein 16 is the intracellular receptor recognizing transfected DNA. Consistently, infection of neutrophils with intracellular pathogens, such as Bartonella henselae, Listeria monocytogenes, Legionella pneumophila, or adenovirus type 5, promoted a marked induction of IFN-ß mRNA expression. Taken together, these data raise questions about the role of PKCε in driving the MyD88-independent/TRIF-dependent response and indicate that human neutrophils are able to recognize and respond to microbial cytosolic DNA. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| Journal | The Journal of Immunology |
| Issue Number | 3 |
| Volume Number | 189 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2012-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Biosynthesis Interferon-beta Neutrophils Immunology Plasmids Genetics Signal Transduction Toll-like Receptor 4 Physiology Transcriptional Activation Up-regulation Adenoviruses, Human Bartonella Henselae Cells, Cultured Cytosol Hek293 Cells Legionella Pneumophila Listeria Monocytogenes Metabolism Microbiology Rna, Messenger Transfection Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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