| First Author | Stemerding AM | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 1 | Pages | 353-62 |
| PubMed ID | 23740955 | Mgi Jnum | J:205457 |
| Mgi Id | MGI:5544888 | Doi | 10.4049/jimmunol.1203243 |
| Citation | Stemerding AM, et al. (2013) Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FLIPr) and its homologue FLIPr-like are potent FcgammaR antagonists that inhibit IgG-mediated effector functions. J Immunol 191(1):353-62 |
| abstractText | 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 FcgammaR-mediated immunity by secreting a potent FcgammaR 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 FcgammaRII receptors, whereas FLIPr-like bound to different FcgammaR subclasses, and both competitively blocked IgG-ligand binding. They fully inhibited FcgammaR-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 FcgammaR-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 FcgammaR-mediated diseases. |
