title: Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients.
abstract: OBJECTIVE
  Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central nervous system. TLRs recognize pathogen- or damage-associated molecular patterns, leading to the release of inflammatory and toxic molecules, which can contribute to neuroinflammation associated with Parkinson's disease (PD). The aim of this study was to compare the potential of peripheral blood cells from PD patients or healthy subjects to produce cytokines after exposure to TLR agonists, and to investigate TLR2 and TLR4 expression on monocyte subsets.
  
  
  METHODS
  Twenty-one patients and 21 healthy controls were recruited. Patients were evaluated according to the Unified Parkinson's Disease Rating Scale, and Hoehn and Yahr stage. Cytokines were measured in supernatants of whole blood cultures after incubation with TLR2, TLR4, or TLR7/8 agonists, by cytometric bead array. Expression of CD14, CD16, TLR2, and TLR4 was analyzed by cytometry.
  
  
  RESULTS
  Patient blood cells produced lower levels of cytokines in response to TLR2 and also after TLR7/8/R848 activation than controls. Percentages of CD14+CD16+ or CD14+CD16- monocytes and TLR2 and TLR4 expression were similar between patients and controls.
  
  
  CONCLUSIONS
  Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD. This was neither associated with imbalance in monocyte subsets nor with TLR2/TLR4 expression on these cells. The association between a decreased TLR response in periphery and damage of brain in PD must be further investigated.
authors.affiliation: Instituto de Patologia Tropical e Sax00FA;de Px00FA;blica, Universidade Federal de Goix00E1;s, Goix00E2;nia, Brazil.
authors.forename: Delson José
authors.initials: DJ
authors.lastname: da Silva
authors.forename: Arissa Felipe
authors.initials: AF
authors.lastname: Borges
authors.forename: Priscila Oliveira
authors.initials: PO
authors.lastname: Souza
authors.forename: Patrícia Reis
authors.initials: PR
authors.lastname: de Souza
authors.forename: Cristina Ribeiro de Barros
authors.initials: CR
authors.lastname: Cardoso
authors.forename: Miriam Leandro
authors.initials: ML
authors.lastname: Dorta
authors.forename: Milton Adriano Pelli
authors.initials: MA
authors.lastname: de Oliveira
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
mesh_terms: D000368:Aged; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000097:blood*; D013223:Statistics as Topic; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007093:Imidazoles; D008070:Lipopolysaccharides; D008074:Lipoproteins; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; C402365:resiquimod