@article{e58fb5d1bcdd45ea8b0958dcbb587296,
title = "Natural Human Immunity Against Staphylococcal Protein A Relies on Effector Functions Triggered by IgG3",
abstract = "Staphylococcal protein A (SpA) is a multifunctional, highly conserved virulence factor of Staphylococcus aureus. By binding the Fc portion of all human IgG subclasses apart from IgG3, SpA interferes with antibody and complement deposition on the bacterial surface, impairing staphylococcal clearance by phagocytosis. Because of its anti-opsonic properties, SpA is not investigated as a surface antigen to mediate bacterial phagocytosis. Herein we investigate human sera for the presence of SpA-opsonizing antibodies. The screening revealed that sera containing IgG3 against SpA were able to correctly opsonize the target and drive Fcγ receptor-mediated interactions and phagocytosis. We demonstrated that IgG3 Fc is significantly more efficient in inducing phagocytosis of SpA-expressing S. aureus as compared to IgG1 Fc in an assay resembling physiological conditions. Furthermore, we show that the capacity of SpA antibodies to induce phagocytosis depends on the specific epitope recognized by the IgGs on SpA molecules. Overall, our results suggest that anti-SpA IgG3 antibodies could favor the anti-staphylococcal response in humans, paving the way towards the identification of a correlate of protection against staphylococcal infections.",
keywords = "IgG3, monoclonal antibodies, phagocytosis, S. aureus, SpA, Humans, Immunoglobulin G, Opsonin Proteins, Staphylococcus, Staphylococcal Protein A, Staphylococcal Infections, Phagocytosis, Staphylococcus aureus, aureus, S",
author = "Elena Boero and Cruz, \{Ana Rita\} and Werner Pansegrau and Cinzia Giovani and Rooijakkers, \{Suzan H.M.\} and \{van Kessel\}, \{Kok P.M.\} and \{van Strijp\}, \{Jos A.G.\} and Fabio Bagnoli and Manetti, \{Andrea G.O.\}",
note = "Funding Information: We thank Isaac Thomsen and Buddy Creech at Vanderbilt University Medical Center (VUMC) for providing the sera used in this study. We thank Silvia Rossi Paccani for the assistance in gaining access to the human sera used in this work. We thank Bruno Galletti and Fabiana Spensieri for their assistance with the Luminex assays, EpiMotion handling, and experiment design. We acknowledge Simona Tavarini and Chiara Sammicheli for their precious assistance with flow cytometry. We thank Elisabetta Frigimelica, Roberta Cozzi, Chiara Limongi, Mariangela Del Vecchio, for their support on the expression and purification of the monoclonal antibodies used in this paper. We thank Maria Stella for the support in data analysis. Funding Information: This work was supported by the European Union{\textquoteright}s Horizon 2020 research: H2020-MSCA-ITN (No. 675106 coordinated by FB, GSK, Siena, Italy) and by GSK. Publisher Copyright: Copyright {\textcopyright} 2022 Boero, Cruz, Pansegrau, Giovani, Rooijakkers, van Kessel, van Strijp, Bagnoli and Manetti. Copyright {\textcopyright} 2022 Boero, Cruz, Pansegrau, Giovani, Rooijakkers, van Kessel, van Strijp, Bagnoli and Manetti.",
year = "2022",
month = mar,
day = "11",
doi = "10.3389/fimmu.2022.834711",
language = "English",
volume = "13",
pages = "1--14",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}