The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases

ten Oever, Jaap; Kox, Matthijs; van de Veerdonk, Frank L; Mothapo, Khutso M; Slavcovici, Adriana; Jansen, Tim L; Tweehuysen, Lieke; Giamarellos-Bourboulis, Evangelos J; Schneeberger, Peter M; Wever, Peter C; Stoffels, Monique; Simon, Anna; van der Meer, Jos WM; Johnson, Melissa D; Kullberg, Bart-Jan; Pickkers, Peter; Pachot, Alexandre; Joosten, Leo AB; Netea, Mihai G

The present study is an important initial proof-ofprinciple report on the role of sTLR2 and sTLR4 during a broad panel of human infections and autoinflammatory diseases. Shedding of sTLR2 and sTLR4 is not confined to stimulation of its corresponding cell surface receptor, but it is a broader effect upon stimulation of innate immune cells through pattern recognition receptors. We report the significant increase of sTLR2 and sTLR4 both in experimental models of human endotoxemia, as well as in the circulation of patients with infections. This suggests an important role of soluble TLRs in the modulation of inflammation during infections and the potential to use these tests as diagnostic markers. Therefore, larger validation studies in larger patient cohorts are warranted in order to be able to draw definitive conclusions regarding the diagnostic usefulness of sTLR2 and sTLR4 in human inflammatory diseases.