TLR2 enhances NADPH oxidase activity and killing of Staphylococcus aureus by PMN

Jann, Naja J.; Schmaler, Mathias; Ferracin, Fabrizia; Landmann, Régine

doi:10.1016/j.imlet.2010.09.007

Cited by 29 publications

(33 citation statements)

References 48 publications

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“…TLR2-deficient mice were hypersusceptible to S. aureus and more slowly cleared subcutaneously inoculated S. aureus than wild-type mice, and peritoneal macrophages derived from the TLR2-deficient mice were insensitive to lipoteichoic acid and heat-killed S. aureus (14). Neutrophils derived from TLR2-deficient mice showed an inability to kill S. aureus, with a defect in the oxidative burst in response to S. aureus, but not phagocytosis (17). Deficiency of TLR2 but not TLR4 increases colonization of a methicillin-resistant S. aureus strain in a mouse model of nasal carriage (12).…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2012

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c 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-killed Staphylococcus aureus and of tumor necrosis factor alpha (TNF-␣) 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 of S. aureus via interfering with its recognition by innate immune cells.

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Section: Discussionmentioning

confidence: 98%

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

et al. 2012

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“…Neutrophils express most of the known TLRs that recognize bacterial structures, most importantly TLR4, which recognizes lipopolysaccharide from Gram-negative bacteria, and TLR2, which recognizes lipoproteins like LTA from Gram-positive bacteria. Stimulation of neutrophils with several TLR ligands stimulates phagocytosis of latex beads (86) and enhance the oxidative burst (87). Neutrophils also express members of the C-type lectins, such as Dectin-1, the receptor for fungal β-glucans and the components of the NLRP3 inflammasome that include the cytoplasmic NOD-like receptors sensing bacterial proteoglycan degradation products and danger signals (88).…”

Section: Neutrophil Primingmentioning

confidence: 99%

Neutrophil-Mediated Phagocytosis of Staphylococcus aureus

2014

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Initial elimination of invading Staphylococcus aureus from the body is mediated by professional phagocytes. The neutrophil is the major phagocyte of the innate immunity and plays a key role in the host defense against staphylococcal infections. Opsonization of the bacteria with immunoglobulins and complement factors enables efficient recognition by the neutrophil that subsequently leads to intracellular compartmentalization and killing. Here, we provide a review of the key processes evolved in neutrophil-mediated phagocytosis of S. aureus and briefly describe killing. As S. aureus is not helpless against the professional phagocytes, we will also highlight its immune evasion arsenal related to phagocytosis.

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“…Signaling through TLR2 activates innate immune cells to phagocytose S. aureus and to signal to the adaptive immune system via the presentation of bacterial antigens [394,395]. Additionally, TLR2 has been shown to activate ROS in immune defenses against S. aureus [396]. The binding of SSL3 to TLR2 inhibits this recognition system allowing S. aureus to avoid immune detection and clearance.…”

Section: The Sialylated Glycan-binding Sslsmentioning

confidence: 99%