Staphylococcal Superantigen-Like Protein 3 Binds to the Toll-Like Receptor 2 Extracellular Domain and Inhibits Cytokine Production Induced by Staphylococcus aureus, Cell Wall Component, or Lipopeptides in Murine Macrophages
Open Access
- 1 August 2012
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 80 (8), 2816-2825
- https://doi.org/10.1128/iai.00399-12
Abstract
Staphylococcal superantigen-like proteins (SSLs) are a family of exoproteins sharing structural similarity with superantigens, but no superantigenic activity. Corresponding host target proteins or receptors against a portion of SSLs in the family have been identified. In this study, we show that SSL3 specifically binds to Toll-like receptor 2 (TLR2) and inhibits the stimulation of macrophages by TLR2 ligands. An approximately 100-kDa protein was recovered by using recombinant His-tagged SSL3-conjugated Sepharose from the lysate of porcine spleen, and the protein was identified as porcine TLR2 by peptide mass fingerprinting analysis. The SSL3-conjugated Sepharose recovered human and mouse TLR2 but not TLR4 from human neutrophils and mouse macrophage RAW 264.7 cells, as well as a recombinant TLR2 extracellular domain chimera protein. The production levels of interleukin 12 (IL-12) from mouse macrophages treated with heat-killedStaphylococcus aureusand of tumor necrosis factor alpha (TNF-α) from RAW 264.7 cells induced by peptidoglycan or lipopeptide TLR2 ligands were strongly suppressed in the presence of SSL3. The mutation of consensus sialic acid-containing glycan-binding residues in SSL3 did not abrogate the binding ability to TLR2 or inhibitory activity on TLR2, indicating that the interaction of SSL3 with TLR2 was independent of the sialic acid-containing glycan-binding residues. These findings demonstrate that SSL3 is able to bind the extracellular domain of TLR2 and interfere with TLR2 function. The present study provides a novel mechanism of SSL3 in immune evasion ofS. aureusvia interfering with its recognition by innate immune cells.Keywords
This publication has 33 references indexed in Scilit:
- Staphylococcal Superantigen-Like Protein 5 Inhibits Matrix Metalloproteinase 9 from Human NeutrophilsInfection and Immunity, 2010
- Specificity of Staphylococcal Superantigen-Like Protein 10 toward the Human IgG1 Fc DomainPublished by The American Association of Immunologists ,2010
- Functional basis for complement evasion by staphylococcal superantigen-like 7Cellular Microbiology, 2010
- TLR2 Mediates Recognition of Live Staphylococcus epidermidis and Clearance of BacteremiaPLOS ONE, 2010
- Treponema denticola Suppresses Expression of Human β-Defensin-3 in Gingival Epithelial Cells through Inhibition of the Toll-Like Receptor 2 AxisInfection and Immunity, 2010
- The crystal structure of staphylococcal superantigen‐like protein 11 in complex with sialyl Lewis X reveals the mechanism for cell binding and immune inhibitionMolecular Microbiology, 2007
- Crystal Structures of the Staphylococcal Toxin SSL5 in Complex with Sialyl Lewis X Reveal a Conserved Binding Site that Shares Common Features with Viral and Bacterial Sialic Acid Binding ProteinsJournal of Molecular Biology, 2007
- CD36 is a sensor of diacylglyceridesNature, 2005
- Toll-like receptor signallingNature Reviews Immunology, 2004
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970