Toll-like receptor 3 differently modulates inflammation in progressive or benign multiple sclerosis |
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Authors: | Marina Saresella Andrea Gatti Paola Tortorella Ivana Marventano Federica Piancone Francesca La Rosa Domenico Caputo Marco Rovaris Mara Biasin Mario Clerici |
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Affiliation: | 1. Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy;2. Department of Clinical Sciences, University of Milano, 20100 Milano, Italy;3. Department of Physiopathology and Transplants, University of Milano, 20100 Milano, Italy |
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Abstract: | TLR-dependent signal transduction pathways were analyzed in patients with a diagnosis of either relapsing–remitting (RRMS), secondary progressive (PMS) or benign (BMS) MS and healthy controls (HC). Prototypical TLR molecules expressed either on the cell surface (TLR4) or intracellularly (TLR3) were stimulated with specific antigens (LPS and poly I:C, respectively). Expression of factors involved in TLR signaling cascades, production of downstream immune mediators and TLR expression were evaluated. Results showed that, whereas LPS-stimulation of TLR4 had a marginal effect on cell activation, poly I:C-stimulated TLR3 expression on immune cells was significantly increased in PMS and BMS compared to HC. This was associated with a higher responsiveness to poly I:C that resulted in the activation of the TLR3-mediated pathway and the production of inflammatory cytokines in PMS and, in contrast, in the up-regulation of a peculiar mosaic of inflammation-dampening genes in BMS. Results herein might explain different MS disease phenotypes. |
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Keywords: | Toll like receptors TLR3 Neuroinflammation Multiple sclerosis Signal transduction |
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