Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components

Abstract

Lipoteichoic acid (LTA) derived from Staphylococcus aureus is reported to be a ligand of Toll-like receptor 2 (TLR2). In this study, we demonstrated that lipoproteins obtained from S. aureus are potent activators of TLR2. A fraction obtained by Triton X-114 phase partitioning activated cells through TLR2. The fraction contained proteins and LTA. The activity was detected in compounds in a mass range of 12-40 kDa. Proteinase K digested the active compounds into lower molecular weight active materials <10 kDa. In contrast, hydrofluoric acid treatment, which decomposes LTA, did not alter the molecular mass of the active compounds. Further, most of the activity was abrogated by lipoprotein lipase digestion. These results suggested that lipoproteins are predominant TLR2 ligands in S. aureus cell wall components.

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

“…Upon contact with the ocular surface with compromised epithelial barrier, S. aureus activates the host cells such as the epithelia and initiates inflammatory response that is essential for containing infection in the cornea [8,19]. S. aureus cell wall-associated and secreted proteins (e.g., lipoproteins, protein A and hemolysins) [20][21][22] and cell wall components (e.g., peptidoglycan and lipoteichoic acid) [23,24] have been shown to cause inflammatory responses and, as such, may contribute to S. aureus keratitis. TLR2 has been shown to play a crucial role in the host response to S. aureus [15].…”

“…TLR2 has been shown to play a crucial role in the host response to S. aureus [15]. Several S. aureus components including lipoteichoic acid (LTA) [25], peptidoglycan [26], and lipoproteins [20,27] were reported to be the ligands of TLR2. However, it is controversial whether LTA and peptidoglycan serve as PAMPs recognized by a cell surface TLR2 [27][28][29].…”

“…In addition to LTA, TLR2 is known to be a predominant receptor utilized by lipoproteins derived from various microorganisms, including both gram-negative bacteria, such as Borrelia burgdorferi, Escherichia coli, Neisseria gonorrhoea, and Porphyromonas gingivalis and Gram positive bacteria S. aureus [20]. Consistent with a recent reports showing that not LTA but lipoproteins are dominant, immunobiologically active TLR2 ligand in S. aureus [20,27], in the present study we showed that the lipoproteins isolated from S. aureus stimulate epithelial cells, leading to the activation of TLR-mediated MAPK and NF-kB signaling pathways, and expression of an array of molecules associated with innate immune response. Thus, we conclude that S. aureus lipoproteins are a major activator of TLR2 in HCECs.…”

“…saLP was isolated according to the method described by Hashimoto et al [20]. S. aureus (strain 8325-4) was grown in a chemically defined medium which is known to enhance the production of cell-wall-associated products at 37 1C with constant shaking (150 rpm) until the late-logarithmic phase (OD600o1).…”

Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3)

“…Among these secreted virulence factors are the staphylococcal superantigen-like proteins (SSLs), a family of 14 proteins located on two genomic clusters (2)(3)(4). Recently, we and others identified SSL3 as a potent inhibitor of Tolllike receptor 2 (TLR2) (5,6), an innate immunity receptor that is a dominant factor in immune recognition of S. aureus (7)(8)(9)(10).…”