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

A. M. Stemerding, M. K. Pandey, A. Kuipers, J. H. Leusen, P. Boross, M. Nederend, G. Vidarsson, A. Y. L. Weersink, J. G. J. van de Winkel, K. P. M. van Kessel, J. A. G. van Strijp, Jörg Köhl

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.
Original languageEnglish
Title of host publicationThe Journal of Immunology
Number of pages10
Publication date01.07.2013
Pages353-362
ISBN (Print)1550-6606 (Electronic)\r0022-1767 (Linking)
DOIs
Publication statusPublished - 01.07.2013

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