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

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.