title: Periodontopathogens induce expression of CD40L on human platelets via TLR2 and TLR4.
abstract: BACKGROUND
  The outstanding importance of (soluble) CD40L to cardiovascular disease (CVD) is becoming increasingly apparent as CD40L is an important mediator of thrombotic and inflammatory processes. Platelets are the main source for CD40 ligand, linking platelet stimulatory events to inflammation and adverse adaptive immune responses. Periodontitis represents a chronic dental infection by distinct gram negative bacteria that is associated with an increased risk for CVD. However, the effects of periodontopathogens on CD40L expression by platelets have not been determined.
  
  
  METHODS
  Effects of periodontopathogens A. actinomycetemcomitans Y and P. gingivalis on the expression of CD40L were determined and the underlying receptors and pathways were investigated. 26 patients with periodontitis and 19 controls were included in the clinical part of this study.
  
  
  RESULTS
  Periodontopathogens directly induce surface expression of CD40L in human platelets. This activation depends on plasma factors like CD14 and involves TLR2 and TLR4 but not FcγRII. Inhibition of PI3K and PLC completely abolishes bacteria-induced surface expression of CD40L. TLR2 and TLR4 agonists, for example, are also able to induce expression and release of CD40L in human platelets. In patients with periodontitis, plasma levels of soluble CD40L are elevated and positivity for P. gingivalis is associated with a statistical significant increase of soluble CD40L.
  
  
  CONCLUSIONS
  Our data indicate an involvement of periodontopathogens in increased plasma levels of soluble CD40L in periodontitis and therefore provide a novel link between periodontitis and increased risk for CVD.
authors.affiliation: Institute of Physiology - Centre for Physiology & Pharmacology, Medical University of Vienna, Austria. alice.assinger@meduniwien.ac.at
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.forename: Markus
authors.initials: M
authors.lastname: Laky
authors.forename: Sigrun
authors.initials: S
authors.lastname: Badrnya
authors.forename: Azadeh
authors.initials: A
authors.lastname: Esfandeyari
authors.forename: Ivo
authors.initials: I
authors.lastname: Volf
mesh_terms: D039903:Actinobacteria / Q000472:pathogenicity*; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D023201:CD40 Ligand / Q000378:metabolism*; D055113:Chronic Periodontitis / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023201:CD40 Ligand