title: Staphylococcal α-toxin induces a functional upregulation of TLR-2 on human peripheral blood monocytes.
abstract: Resistance to bacterial skin infections, for example with Staphylococcus aureus (S. aureus), is based on the function of intact innate immune mechanisms. Toll-like receptor (TLR)-2 recognizes components of S. aureus and is known to be expressed on monocytes. Staphylococcal exotoxins such as staphylococcal enterotoxin B (SEB) or α-toxin are produced by many S. aureus strains. To investigate TLR-2 regulation and function on human monocytes upon stimulation with staphylococcal exotoxins to elucidate a putative feedback loop between different staphylococcal components. Monocytes were stimulated with α-toxin or SEB, respectively. TLR-2 expression and regulation as well as functional effects of TLR-2 stimulation with Pam3Cys (TLR-2/TLR-1), lipoteichoic acid (LTA) (TLR-2/TLR-6) and peptidoglycan (PGN) (TLR-2 and Nod) were then investigated both at the mRNA and protein level and compared to monocytes from patients with psoriasis. α-toxin significantly upregulated TLR-2 expression. TLR-2 mediated IL-1β, IL-6 and IL-8 secretion was significantly augmented after upregulation with staphylococcal exotoxins. CD36 expression was significantly more downregulated after TLR-2 upregulation with SEB and consecutive LTA stimulation and TLR-2 upregulation with α-toxin following LTA and PGN stimulation, respectively. PGN enhanced CD54 expression after upregulation of the receptor with α-toxin. Expression of HLA-DR was unaffected. However, no differences were observed in monocytes from psoriasis patients compared to healthy controls. Together, our findings provide a new link between staphylococcal α-toxin and TLR-2 signalling in monocytes which may have implications for skin diseases where skin colonization with S. aureus and dysregulation of TLR-2 have been described.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Margarete
authors.initials: M
authors.lastname: Niebuhr
authors.forename: Kartinka
authors.initials: K
authors.lastname: Schorling
authors.forename: Annice
authors.initials: A
authors.lastname: Heratizadeh
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D018955:CD36 Antigens / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D006460:Hemolysin Proteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013207:Staphylococcal Skin Infections / Q000209:etiology / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000097:blood* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D001427:Bacterial Toxins; D018955:CD36 Antigens; C508606:CXCL8 protein, human; D004768:Enterotoxins; D006460:Hemolysin Proteins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C021091:staphylococcal alpha-toxin; C031818:enterotoxin B, staphylococcal
keywords: SEB; TLR-2; human; monocyte; α-toxin