Abstract |
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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Authors | Annette M Stemerding, Jörg Köhl, Manoj K Pandey, Annemarie Kuipers, Jeanette H Leusen, Peter Boross, Maaike Nederend, Gestur Vidarsson, Annemarie Y L Weersink, Jan G J van de Winkel, Kok P M van Kessel, Jos A G van Strijp |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 191
Issue 1
Pg. 353-62
(Jul 01 2013)
ISSN: 1550-6606 [Electronic] United States |
PMID | 23740955
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bacterial Proteins
- FPRL1 inhibitory protein, S aureus
- Fc gamma receptor IIA
- Receptors, IgG
- chemotaxis inhibitory protein, Staphylococcus aureus
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Topics |
- Animals
- Antibody-Dependent Cell Cytotoxicity
(immunology)
- Bacterial Proteins
(chemistry, metabolism, physiology)
- Binding Sites, Antibody
(immunology)
- Humans
- Immune Evasion
(immunology)
- Leukemia P388
(immunology, microbiology)
- Mice
- Mice, Inbred BALB C
- Phagocytosis
(immunology)
- Protein Binding
(immunology)
- Receptors, IgG
(antagonists & inhibitors, chemistry, physiology)
- Sequence Homology, Amino Acid
- Staphylococcal Infections
(immunology, microbiology, prevention & control)
- Staphylococcus aureus
(growth & development, immunology, pathogenicity)
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