Staphylococcal α‐toxin induces a functional upregulation of TLR‐2 on human peripheral blood monocytes

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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.

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