Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FLIPr) and its homologue FLIPr-like are potent FcγR antagonists that inhibit IgG-mediated effector functions.

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.

• 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)

Chemical References

• Bacterial Proteins
• FPRL1 inhibitory protein, S aureus
• Fc gamma receptor IIA
• Receptors, IgG
• chemotaxis inhibitory protein, Staphylococcus aureus

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)