title: Impaired toll-like receptor 8 signaling in multiple sclerosis.
abstract: BACKGROUND
  The etiology and immunopathology of multiple sclerosis (MS) is not well understood. It is recognized that although autoreactive T cells are the main early mediators of disease, other cell types, including cells of the innate immune system contribute to MS pathogenesis. The objective of this study was to determine if Toll-like receptor (TLR) signaling is functionally altered in patients with MS.
  
  
  RESULTS
  Peripheral blood mononuclear cells from healthy donors and patients with relapsing remitting MS were stimulated with specific agonists of TLRs 3, 7, 8 and 9. Using quantitative polymerase chain reaction transcript levels of tumor necrosis factor-α, interferon-α and interleukin (IL)-12β were quantified from patients with MS and healthy donors. TLR8-induced production of IL12B transcripts and protein was functionally impaired in patients with MS as compared to healthy controls (P <0.05 and P <0.005, respectively). Patients with MS also expressed lower baseline levels of TLR8 as compared to healthy controls (P <0.05).
  
  
  CONCLUSIONS
  TLR8 expression and signaling is impaired in peripheral blood mononuclear cells from patients with MS. This finding suggests that loss of TLR8 signaling may be contributing to autoimmune processes in MS.
authors.affiliation: Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg 10, 7C-103, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Tory P
authors.initials: TP
authors.lastname: Johnson
authors.forename: Richa
authors.initials: R
authors.lastname: Tyagi
authors.forename: Karan
authors.initials: K
authors.lastname: Patel
authors.forename: Nicoline
authors.initials: N
authors.lastname: Schiess
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D051196:Toll-Like Receptor 3; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases