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

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.

Diagnosis of ocular toxocariasis by establishing intraocular antibody production.

PURPOSE: To investigate the role of Toxocara canis in posterior uveitis of undetermined origin. DESIGN: Retrospective case-study. METHODS: Paired ocular fluid (47 aqueous humor [AH] and two vitreous fluids) and serum samples of 37 adults and 12 children with undetermined posterior uveitis were retrospectively analyzed for intraocular IgG antibody production against Toxocara canis by enzyme-linked immunosorbent assay and Goldmann-Witmer coefficient (GWC) determination. Previous diagnostic investigation by polymerase chain reaction and GWC for Herpes simplex virus, Varicella zoster virus, and Toxoplasma gondii had not provided a cause of the posterior uveitis. RESULTS: Three of 12 (25%) children showed intraocular IgG production against Toxocara canis. One child had vitritis, one presented with a low-grade uveitis and a peripheral retinal lesion, and the third had posterior uveitis and a chorioretinal scar. All three children had AH IgG titers exceeding those of the corresponding serum. In fact, two children had low Toxocara serum IgG titers (<1:32) and would have been considered seronegative upon routine serology screening. Intraocular antibody production against Toxocara canis was absent in all 37 adults, including five seropositive patients. CONCLUSIONS: Our results indicate that ocular toxocariasis is mainly a pediatric disease. Serological screening is not informative for the diagnosis of intraocular Toxocara infection. Toxocara GWC analysis, however, can be of value when diagnosing patients with posterior focal lesions or vitritis of unknown etiology.