A New Staphylococcal Anti-Inflammatory Protein That Antagonizes the Formyl Peptide Receptor-Like 1

Prat, Cristina; Bestebroer, Jovanka; Haas, Carla J. C. de; Strijp, Jos A. G. van; Kessel, Kok P. M. van

doi:10.4049/jimmunol.177.11.8017

Cited by 112 publications

(121 citation statements)

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“…Fluorescent intensities were measured by flow cytometry and expressed relative to control cells not exposed to supernatant or recombinant protein. FLIPr and FLIPr-like were labeled with FITC, as described (21,22), and incubated with leukocytes in the presence of specific markers for monocytes (PE-labeled anti-CD14), T cells (allophycocyanin-labeled anti-CD3), B cells (PE-labeled anti-CD19), or NK cells (PE-labeled CD56 and allophycocyanin-labeled anti-CD3). Cells were gated by their scatter and marker profile.…”

Section: Cells and Flow Cytometry Stainingmentioning

confidence: 99%

“…Human neutrophils and mononuclear cells were isolated from heparinized blood, as described (21). Cells were incubated with staphylococcal supernatants (30% v/v) or purified recombinant proteins for 0-10 min on ice, washed, and subsequently stained with fluorescent mAb.…”

Section: Cells and Flow Cytometry Stainingmentioning

confidence: 99%

“…The recombinant staphylococcal proteins FLIPr, FLIPr-like, and CHIPS were expressed and purified from Escherichia coli, as described (20)(21)(22).…”

Section: Bacterial Supernatants and Proteinsmentioning

confidence: 99%

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Staphylococcus aureus Formyl Peptide Receptor–like 1 Inhibitor (FLIPr) and Its Homologue FLIPr-like Are Potent FcγR Antagonists That Inhibit IgG-Mediated Effector Functions

Stemerding

Köhl

Pandey

et al. 2013

The Journal of Immunology

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To evade opsonophagocytosis, Staphylococcus aureus secretes various immunomodulatory molecules that interfere with effective opsonization by complement and/or IgG. Immune-evasion molecules targeting the phagocyte receptors for these opsonins have not been described. In this study, we demonstrate that S. aureus escapes from FcγR-mediated immunity by secreting a potent FcγR antagonist, FLIPr, or its homolog FLIPr-like. Both proteins were previously reported to function as formyl peptide receptor inhibitors. Binding of FLIPr was mainly restricted to FcγRII receptors, whereas FLIPr-like bound to different FcγR subclasses, and both competitively blocked IgG-ligand binding. They fully inhibited FcγR-mediated effector functions, including opsonophagocytosis and subsequent intracellular killing of S. aureus by neutrophils and Ab-dependent cellular cytotoxicity of tumor cells by both neutrophils and NK cells. In vivo, treatment of mice with FLIPr-like prevented the development of an immune complex–mediated FcγR-dependent Arthus reaction. This study reveals a novel immune-escape function for S. aureus–secreted proteins that may lead to the development of new therapeutic agents in FcγR-mediated diseases.

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Section: Cells and Flow Cytometry Stainingmentioning

confidence: 99%

Section: Cells and Flow Cytometry Stainingmentioning

confidence: 99%

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Staphylococcus aureus Formyl Peptide Receptor–like 1 Inhibitor (FLIPr) and Its Homologue FLIPr-like Are Potent FcγR Antagonists That Inhibit IgG-Mediated Effector Functions

Stemerding

Köhl

Pandey

et al. 2013

The Journal of Immunology

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“…aureus has some special proteins that may have an effect on innate and acquired immunity. Staphylococcal complement inhibitor, chemotaxis-inhibitory protein of S. aureus, staphylokinase, extracellular fibrinogen-binding protein, extracellular adherence protein, and formyl peptide receptor like-1 inhibitory protein are some of these special proteins (21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

PCR investigation of Panton-Valentine leukocidin, enterotoxin, exfoliative toxin,and agr genes in Staphylococcus aureus strains isolated from psoriasis patients*

Göçmen¹,

Sahiner²,

Koçak³

et al. 2015

Turk J Med Sci

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IntroductionPsoriasis is a chronic inflammatory disorder involving the skin. Genetic, environmental, and immunological factors play important roles in the development of the disease. Its incidence may change in different parts of the world depending on environmental, ethnic, and geographic differences. Both sexes are affected equally by the disease, and patients are usually diagnosed between 15 and 30 years of age. Although it can be seen in almost all races, it is rare in Asia and Africa. It has an overall prevalence of 2%-3% in the general population (1,2). Its prevalence in children is reported to range from 0% (Taiwan) to 2.1% (Italy), and in adults from 0.91% (United States) to 8.5% (Norway). In the United States, the annual incidence estimate in children is 40.8/100,000, while in adults the annual incidence varies from 78.9/100,000 (United States) to 230/100,000 (Italy) (1). The prevalence in the Turkish population is reported as 1.3% (2). Bacteria are known to play an important role in the development and chronicity of chronic inflammatory diseases such as atopic dermatitis and psoriasis. The relationship between bacterial colonization or infection of the skin and the development of inflammatory skin diseases is well described in studies reporting the relapse of guttate psoriasis following streptococcal pharyngitis and the development of atopic dermatitis following Staphylococcus aureus colonization of the skin (3,4).S. aureus colonizes the anterior nares of 20%-40% of the healthy adult population. It can also colonize the perineum, perianal region, axilla, gastrointestinal tract, and skin folds. Trauma, burns, diabetes, and immune suppression can lead to opportunistic infections with this colonizing pathogen (5).S. aureus can be the cause of a wide spectrum of infectious diseases due to its many virulence factors, which facilitate its spread in host tissues and its escape Background/aim: Staphylococcus aureus colonization is a determiner of disease activation in psoriasis patients. Here we evaluate the presence of genes encoding Panton-Valentine leukocidin (PVL), enterotoxins, TSST-1, exfoliative toxins, and the accessory gene regulatory locus by polymerase chain reaction (PCR) in S. aureus isolates obtained from healthy and diseased skin regions and anterior nares of psoriasis patients and healthy controls. Materials and methods:The presence of PVL and toxin genes was investigated, and agr typing was performed by PCR.Results: Eighteen of the isolated strains carried the sei, 1 carried the seb-sec, and 1 carried the seg enterotoxin gene. Eight of the strains carrying enterotoxin genes were isolated from nasal swabs, 6 from diseased skin swabs, and 4 from healthy skin swabs. None of the strains isolated from the control group carried the agr locus. On the other hand, 11 of the S. aureus strains isolated from the patients carried type 1, 7 carried type 1 + 3, 4 carried type 2, 4 carried type 3, and 1 carried type 1 + 2 agr loci. Conclusion:Enterotoxin production and the carried accessory gene regulatory loc...

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“…Using this method, it is possible to study the direct effects of toxic and other components on neutrophils, and determine the lowest concentration at which these are active. For us, it is a very useful tool to study the effect of many proteins produced by S. aureus involved in immune evasion, such as FPR2 inhibitory protein (FLIPr) 8 , FLIPr-like 7 , and Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) 9 . All these proteins have been shown to inhibit the calcium mobilization in neutrophils by binding to the receptor recognizing the agonist.…”

Section: Introductionmentioning

confidence: 99%

Studying Interactions of <em>Staphylococcus aureus</em> with Neutrophils by Flow Cytometry and Time Lapse Microscopy

Surewaard

Strijp

Nijland

2013

JoVE

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We present methods to study the effect of phenol soluble modulins (PSMs) and other toxins produced and secreted by Staphylococcus aureus on neutrophils. To study the effects of the PSMs on neutrophils we isolate fresh neutrophils using density gradient centrifugation. These neutrophils are loaded with a dye that fluoresces upon calcium mobilization. The activation of neutrophils by PSMs initiates a rapid and transient increase in the free intracellular calcium concentration. In a flow cytometry experiment this rapid mobilization can be measured by monitoring the fluorescence of a pre-loaded dye that reacts to the increased concentration of free Ca 2+. Using this method we can determine the PSM concentration necessary to activate the neutrophil, and measure the effects of specific and general inhibitors of the neutrophil activation.To investigate the expression of the PSMs in the intracellular space, we have constructed reporter fusions of the promoter of the PSMα operon to GFP. When these reporter strains of S. aureus are phagocytosed by neutrophils, the induction of expression can be observed using fluorescence microscopy. Video LinkThe video component of this article can be found at

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A New Staphylococcal Anti-Inflammatory Protein That Antagonizes the Formyl Peptide Receptor-Like 1

Cited by 112 publications

References 59 publications

Staphylococcus aureus Formyl Peptide Receptor–like 1 Inhibitor (FLIPr) and Its Homologue FLIPr-like Are Potent FcγR Antagonists That Inhibit IgG-Mediated Effector Functions

Staphylococcus aureus Formyl Peptide Receptor–like 1 Inhibitor (FLIPr) and Its Homologue FLIPr-like Are Potent FcγR Antagonists That Inhibit IgG-Mediated Effector Functions

PCR investigation of Panton-Valentine leukocidin, enterotoxin, exfoliative toxin,and agr genes in Staphylococcus aureus strains isolated from psoriasis patients*

Studying Interactions of <em>Staphylococcus aureus</em> with Neutrophils by Flow Cytometry and Time Lapse Microscopy

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