title: Recognition of Propionibacterium acnes by human TLR2 heterodimers.
abstract: Propionibacterium acnes has been considered as a crucial contributor to the pathogenesis of acne vulgaris. The interaction between P. acnes and the host is mainly mediated by Toll like receptor (TLR) 2 recognition. TLR2 homodimers recognize P. acnes in mice, but here we describe the prerequisite of TLR2/1 and TLR2/6 heterodimers in human cells for P. acnes recognition. P. acnes-induced NF-κB and AP-1activation observed in HEK hTLR2-transfected but not control cells confirmed the specificity of TLR2 recognition. The activation was blocked by neutralizing antibodies against TLR2, TLR1 and TLR6, as well as the TLR2 antagonist CU-CPT22, which showed no selectivity towards human TLR2 heterodimers. The combination of anti-TLR1 and anti-TLR6 antibodies completely abrogated activation by P. acnes. In primary human keratinocytes, P. acnes-increased NF-κB phosphorylation was inhibited by anti-TLR6 and anti-TLR2 antibodies. Furthermore, P. acnes-induced inflammatory responses were impaired by anti-TLR2 neutralizing antibodies and fully blocked by CU-CPT22. Our study suggests species-specific recognition of P. acnes by TLR2 heterodimers which can be exploited therapeutically by small molecules targeting TLR2 for the control of inflammatory responses.
authors.affiliation: Freie Universität Berlin, Institute of Pharmacy (Pharmacology and Toxicology), Berlin, Germany.
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
authors.affiliation: Freie Universität Berlin, Institute of Pharmacy (Pharmacology and Toxicology), Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Grabowski
authors.affiliation: Freie Universität Berlin, Institute of Pharmacy (Pharmacology and Toxicology), Berlin, Germany. Electronic address: Guenther.Weindl@fu-berlin.de.
authors.forename: Günther
authors.initials: G
authors.lastname: Weindl
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology*; D011485:Protein Binding; D055503:Protein Multimerization; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000378:metabolism
chemical_list: C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6
keywords: Inflammation; Propionibacterium acnes; TLR2 antagonists; TLR2 heterodimers; Toll-like receptors