Toll-like receptor 3 differently modulates inflammation in progressive or benign multiple sclerosis

Marina Saresella, Andrea Gatti, Paola Tortorella, Ivana Marventano, Federica Piancone, Francesca La Rosa, Domenico Caputo, Marco Rovaris, Mara Biasin, Mario Clerici

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)109-120
Number of pages12
JournalClinical Immunology
Volume150
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Multiple sclerosis
  • Neuroinflammation
  • Signal transduction
  • TLR3
  • Toll like receptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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