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1. Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation

Author

van der Lans, Sjors P. A., Bardoel, Bart W., Ruyken, Maartje, de Haas, Carla J. C., Baijens, Stan, Muts, Remy M., Scheepmaker, Lisette M., Aerts, Piet C., van ’t Wout, Marije F. L., Preiner, Johannes, Marijnissen, Renoud J., Schuurman, Janine, Beurskens, Frank J., Kerkman, Priscilla F., and Rooijakkers, Suzan H. M.

Published
2024
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2. Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Author

Hendriks, Astrid, Kerkman, Priscilla F., Varkila, Meri R.J., Haitsma Mulier, Jelle L.G., Ali, Sara, ten Doesschate, Thijs, van der Vaart, Thomas W., de Haas, Carla J.C., Aerts, Piet C., Cremer, Olaf L., Bonten, Marc J.M., Nizet, Victor, Liu, George Y., Codée, Jeroen D.C., Rooijakkers, Suzan H.M., van Strijp, Jos A.G., and van Sorge, Nina M.

Published
2024
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4. C1q binding to surface-bound IgG is stabilized by C1r₂s₂ proteases

Author

Zwarthoff, Seline A., Widmer, Kevin, Kuipers, Annemarie, Strasser, Jürgen, Ruyken, Maartje, Aerts, Piet C., de Haas, Carla J. C., Ugurlar, Deniz, den Boer, Maurits A., Vidarsson, Gestur, van Strijp, Jos A. G., Gros, Piet, Parren, Paul W. H. I., van Kessel, Kok P. M., Preiner, Johannes, Beurskens, Frank J., Schuurman, Janine, Ricklin, Daniel, and Rooijakkers, Suzan H. M.

Published
2021

6. Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection

Author

Dijk, Bruce van, primary, Oliveira, Sabrina, additional, Hooning van Duyvenbode, J. Fred F., additional, Nurmohamed, F. Ruben H. A., additional, Mashayekhi, Vida, additional, Hernández, Irati Beltrán, additional, van Strijp, Jos, additional, de Vor, Lisanne, additional, Aerts, Piet C., additional, Vogely, H. Charles, additional, Weinans, Harrie, additional, and van der Wal, Bart C. H., additional

Published
2024
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7. Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation

Author

MMB Research line 1, Infection & Immunity, MMB Onderzoek en Onderwijs, CTI, van der Lans, Sjors P A, Bardoel, Bart W, Ruyken, Maartje, de Haas, Carla J C, Baijens, Stan, Muts, Remy M, Scheepmaker, Lisette M, Aerts, Piet C, van 't Wout, Marije F L, Preiner, Johannes, Marijnissen, Renoud J, Schuurman, Janine, Beurskens, Frank J, Kerkman, Priscilla F, Rooijakkers, Suzan H M, MMB Research line 1, Infection & Immunity, MMB Onderzoek en Onderwijs, CTI, van der Lans, Sjors P A, Bardoel, Bart W, Ruyken, Maartje, de Haas, Carla J C, Baijens, Stan, Muts, Remy M, Scheepmaker, Lisette M, Aerts, Piet C, van 't Wout, Marije F L, Preiner, Johannes, Marijnissen, Renoud J, Schuurman, Janine, Beurskens, Frank J, Kerkman, Priscilla F, and Rooijakkers, Suzan H M

Published
2024

8. Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Author

MMB Research line 1, Infection & Immunity, Sepsis and Inflammation, Epi Infectieziekten Team 1, JC onderzoeksprogramma Infectious Diseases, Medische Staf Intensive Care, Epi Infectieziekten, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, MMB Onderzoek en Onderwijs, Hendriks, Astrid, Kerkman, Priscilla F, Varkila, Meri R J, Haitsma Mulier, Jelle L G, Ali, Sara, Ten Doesschate, Thijs, van der Vaart, Thomas W, de Haas, Carla J C, Aerts, Piet C, Cremer, Olaf L, Bonten, Marc J M, Nizet, Victor, Liu, George Y, Codée, Jeroen D C, Rooijakkers, Suzan H M, van Strijp, Jos A G, van Sorge, Nina M, MMB Research line 1, Infection & Immunity, Sepsis and Inflammation, Epi Infectieziekten Team 1, JC onderzoeksprogramma Infectious Diseases, Medische Staf Intensive Care, Epi Infectieziekten, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, MMB Onderzoek en Onderwijs, Hendriks, Astrid, Kerkman, Priscilla F, Varkila, Meri R J, Haitsma Mulier, Jelle L G, Ali, Sara, Ten Doesschate, Thijs, van der Vaart, Thomas W, de Haas, Carla J C, Aerts, Piet C, Cremer, Olaf L, Bonten, Marc J M, Nizet, Victor, Liu, George Y, Codée, Jeroen D C, Rooijakkers, Suzan H M, van Strijp, Jos A G, and van Sorge, Nina M

Published
2024

9. Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection

Author

ORT Research, MMB Onderzoek en Onderwijs, Infection & Immunity, MMB Research line 1, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Dijk, Bruce van, Oliveira, Sabrina, Hooning van Duyvenbode, J Fred F, Nurmohamed, F Ruben H A, Mashayekhi, Vida, Hernández, Irati Beltrán, van Strijp, Jos, de Vor, Lisanne, Aerts, Piet C, Vogely, H Charles, Weinans, Harrie, van der Wal, Bart C H, ORT Research, MMB Onderzoek en Onderwijs, Infection & Immunity, MMB Research line 1, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Dijk, Bruce van, Oliveira, Sabrina, Hooning van Duyvenbode, J Fred F, Nurmohamed, F Ruben H A, Mashayekhi, Vida, Hernández, Irati Beltrán, van Strijp, Jos, de Vor, Lisanne, Aerts, Piet C, Vogely, H Charles, Weinans, Harrie, and van der Wal, Bart C H

Published
2024

10. Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection

Author

Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, Dijk, Bruce van, Oliveira, Sabrina, Hooning van Duyvenbode, J Fred F, Nurmohamed, F Ruben H A, Mashayekhi, Vida, Hernández, Irati Beltrán, van Strijp, Jos, de Vor, Lisanne, Aerts, Piet C, Vogely, H Charles, Weinans, Harrie, van der Wal, Bart C H, Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, Dijk, Bruce van, Oliveira, Sabrina, Hooning van Duyvenbode, J Fred F, Nurmohamed, F Ruben H A, Mashayekhi, Vida, Hernández, Irati Beltrán, van Strijp, Jos, de Vor, Lisanne, Aerts, Piet C, Vogely, H Charles, Weinans, Harrie, and van der Wal, Bart C H

Published
2024

12. CD5L is a canonical component of circulatory IgM

Author

Oskam, Nienke, primary, den Boer, Maurits A., additional, Lukassen, Marie V., additional, Ooijevaar-de Heer, Pleuni, additional, Veth, Tim S., additional, van Mierlo, Gerard, additional, Lai, Szu-Hsueh, additional, Derksen, Ninotska I. L., additional, Yin, Victor, additional, Streutker, Marij, additional, Franc, Vojtech, additional, Šiborová, Marta, additional, Damen, Mirjam J. A., additional, Kos, Dorien, additional, Barendregt, Arjan, additional, Bondt, Albert, additional, van Goudoever, Johannes B., additional, de Haas, Carla J. C., additional, Aerts, Piet C., additional, Muts, Remy M., additional, Rooijakkers, Suzan H. M., additional, Vidarsson, Gestur, additional, Rispens, Theo, additional, and Heck, Albert J. R., additional

Published
2023
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14. Glycan-specific IgM is critical for human immunity toStaphylococcus aureus

Author

Hendriks, Astrid, primary, Kerkman, Priscilla F., additional, Varkila, Meri R.J., additional, Haitsma-Mulier, Jelle L.G., additional, Ali, Sara, additional, ten Doesschate, Thijs, additional, van der Vaart, Thomas W., additional, de Haas, Carla J.C., additional, Aerts, Piet C., additional, Cremer, Olaf L., additional, Bonten, Marc J.M., additional, Nizet, Victor, additional, Liu, George Y., additional, Codée, Jeroen D.C., additional, Rooijakkers, Suzan H.M., additional, van Strijp, Jos A.G., additional, and van Sorge, Nina M., additional

Published
2023
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15. Artificial surface labelling of Escherichia coli with StrepTagII antigen to study how monoclonal antibodies drive complement-mediated killing

Author

Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, Heesterbeek, Dani A C, Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, and Heesterbeek, Dani A C

Abstract

Antibodies play a key role in the immune defence against Gram-negative bacteria. After binding to bacterial surface antigens, IgG and IgM can activate the complement system and trigger formation of lytic membrane attack complex (MAC) pores. Molecular studies to compare functional activity of antibodies on bacteria are hampered by the limited availability of well-defined antibodies against bacterial surface antigens. Therefore, we genetically engineered E. coli by expressing the StrepTagII antigen into outer membrane protein X (OmpX) and validated that these engineered bacteria were recognised by anti-StrepTagII antibodies. We then combined this antigen-antibody system with a purified complement assay to avoid interference of serum components and directly compare MAC-mediated bacterial killing via IgG1 and pentameric IgM. While both IgG1 and IgM could induce MAC-mediated killing, we show that IgM has an increased capacity to induce complement-mediated killing of E. coli compared to IgG1. While Fc mutations that enhance IgG clustering after target binding could not improve MAC formation, mutations that cause formation of pre-assembled IgG hexamers enhanced the complement activating capacity of IgG1. Altogether, we here present a system to study antibody-dependent complement activation on E. coli and show IgM's enhanced capacity over IgG to induce complement-mediated lysis of E. coli.

Published
2023

16. Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae.

Author

Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, Rooijakkers, Suzan H M, Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, and Rooijakkers, Suzan H M

Abstract

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and an important cause of childhood mortality. Despite the introduction of successful vaccines, the global spread of both non-vaccine serotypes and antibiotic-resistant strains reinforces the development of alternative therapies against this pathogen. One possible route is the development of monoclonal antibodies (mAbs) that induce killing of bacteria via the immune system. Here, we investigate whether mAbs can be used to induce killing of pneumococcal serotypes for which the current vaccines show unsuccessful protection. Our study demonstrates that when human mAbs against pneumococcal capsule polysaccharides (CPS) have a poor capacity to induce complement activation, a critical process for immune protection against pneumococci, their activity can be strongly improved by hexamerization-enhancing mutations. Our data indicate that anti-capsular antibodies may have a low capacity to form higher-order oligomers (IgG hexamers) that are needed to recruit complement component C1. Indeed, specific point mutations in the IgG-Fc domain that strengthen hexamerization strongly enhance C1 recruitment and downstream complement activation on encapsulated pneumococci. Specifically, hexamerization-enhancing mutations E430G or E345K in CPS6-IgG strongly potentiate complement activation on S. pneumoniae strains that express capsular serotype 6 (CPS6), and the highly invasive serotype 19A strain. Furthermore, these mutations improve complement activation via mAbs recognizing CPS3 and CPS8 strains. Importantly, hexamer-enhancing mutations enable mAbs to induce strong opsonophagocytic killing by human neutrophils. Finally, passive immunization with CPS6-IgG1-E345K protected mice from developing severe pneumonia. Altogether, this work provides an important proof of concept for future optimization of antibody therapies against encapsulated bacteria.

Published
2023

17. Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae.

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, Rooijakkers, Suzan H M, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, and Rooijakkers, Suzan H M

Published
2023

18. CD5L is a canonical component of circulatory IgM

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Oskam, Nienke, den Boer, Maurits A., Lukassen, Marie V., Ooijevaar-De Heer, Pleuni, Veth, Tim S., van Mierlo, Gerard, Lai, Szu Hsueh, Derksen, Ninotska I.L., Yin, Victor, Streutker, Marij, Franc, Vojtech, Šiborová, Marta, Damen, Mirjam J.A., Kos, Dorien, Barendregt, Arjan, Bondt, Albert, van Goudoever, Johannes B., de Haas, Carla J.C., Aerts, Piet C., Muts, Remy M., Rooijakkers, Suzan H.M., Vidarsson, Gestur, Rispens, Theo, Heck, Albert J.R., Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Oskam, Nienke, den Boer, Maurits A., Lukassen, Marie V., Ooijevaar-De Heer, Pleuni, Veth, Tim S., van Mierlo, Gerard, Lai, Szu Hsueh, Derksen, Ninotska I.L., Yin, Victor, Streutker, Marij, Franc, Vojtech, Šiborová, Marta, Damen, Mirjam J.A., Kos, Dorien, Barendregt, Arjan, Bondt, Albert, van Goudoever, Johannes B., de Haas, Carla J.C., Aerts, Piet C., Muts, Remy M., Rooijakkers, Suzan H.M., Vidarsson, Gestur, Rispens, Theo, and Heck, Albert J.R.

Published
2023

19. Artificial surface labelling of Escherichia coli with StrepTagII antigen to study how monoclonal antibodies drive complement-mediated killing

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, Heesterbeek, Dani A C, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, and Heesterbeek, Dani A C

Published
2023

20. CD5L is a canonical component of circulatory IgM

Author

MMB Research line 1, Infection & Immunity, Oskam, Nienke, den Boer, Maurits A, Lukassen, Marie V, Ooijevaar-de Heer, Pleuni, Veth, Tim S, van Mierlo, Gerard, Lai, Szu-Hsueh, Derksen, Ninotska I L, Yin, Victor, Streutker, Marij, Franc, Vojtech, Šiborová, Marta, Damen, Mirjam J A, Kos, Dorien, Barendregt, Arjan, Bondt, Albert, van Goudoever, Johannes B, de Haas, Carla J C, Aerts, Piet C, Muts, Remy M, Rooijakkers, Suzan H M, Vidarsson, Gestur, Rispens, Theo, Heck, Albert J R, MMB Research line 1, Infection & Immunity, Oskam, Nienke, den Boer, Maurits A, Lukassen, Marie V, Ooijevaar-de Heer, Pleuni, Veth, Tim S, van Mierlo, Gerard, Lai, Szu-Hsueh, Derksen, Ninotska I L, Yin, Victor, Streutker, Marij, Franc, Vojtech, Šiborová, Marta, Damen, Mirjam J A, Kos, Dorien, Barendregt, Arjan, Bondt, Albert, van Goudoever, Johannes B, de Haas, Carla J C, Aerts, Piet C, Muts, Remy M, Rooijakkers, Suzan H M, Vidarsson, Gestur, Rispens, Theo, and Heck, Albert J R

Published
2023

21. Artificial surface labelling of Escherichia coli with StrepTagII antigen to study how monoclonal antibodies drive complement-mediated killing

Author

MMB Research line 1, Infection & Immunity, Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, Heesterbeek, Dani A C, MMB Research line 1, Infection & Immunity, Muts, Remy M, den Boer, Maurits A, Bardoel, Bart W, Aerts, Piet C, de Haas, Carla J C, Heck, Albert J R, Rooijakkers, Suzan H M, and Heesterbeek, Dani A C

Published
2023

22. Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae.

Author

MMB Research line 1, Infection & Immunity, MMB, Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, Rooijakkers, Suzan H M, MMB Research line 1, Infection & Immunity, MMB, Aguinagalde Salazar, Leire, den Boer, Maurits A, Castenmiller, Suzanne M, Zwarthoff, Seline A, de Haas, Carla, Aerts, Piet C, Beurskens, Frank J, Schuurman, Janine, Heck, Albert J R, van Kessel, Kok, and Rooijakkers, Suzan H M

Published
2023

23. Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae

Author

Aguinagalde Salazar, Leire, primary, den Boer, Maurits A, additional, Castenmiller, Suzanne M, additional, Zwarthoff, Seline A, additional, de Haas, Carla, additional, Aerts, Piet C, additional, Beurskens, Frank J, additional, Schuurman, Janine, additional, Heck, Albert JR, additional, van Kessel, Kok, additional, and Rooijakkers, Suzan HM, additional

Published
2023
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25. Glycan-Specific IgM Is Critical for Human Immunity to Staphylococcus aureus

Author

Hendriks, Astrid, primary, Kerkman, Priscilla F., additional, Varkila, Meri R.J., additional, Haitsma-Mulier, Jelle L.G., additional, Ali, Sara, additional, ten Doesschate, Thijs, additional, van der Vaart, Thomas W., additional, de Haas, Carla J.C., additional, Aerts, Piet C., additional, Cremer, Olaf L., additional, Bonten, Marc J.M., additional, Nizet, Victor, additional, Liu, George Y., additional, Codée, Jeroen D.C., additional, Rooijakkers, Suzan H.M., additional, van Strijp, Jos, additional, and van Sorge, Nina M., additional

Published
2023
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26. Toward Understanding How Staphylococcal Protein A Inhibits IgG-Mediated Phagocytosis

Author

Cruz, Ana Rita, Bentlage, Arthur E H, Blonk, Robin, de Haas, Carla J C, Aerts, Piet C, Scheepmaker, Lisette M, Bouwmeester, Inge G, Lux, Anja, van Strijp, Jos A G, Nimmerjahn, Falk, van Kessel, Kok P M, Vidarsson, Gestur, Rooijakkers, Suzan H M, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, AII - Inflammatory diseases, Landsteiner Laboratory, Afd Biomol.Mass Spect. and Proteomics, and Biomolecular Mass Spectrometry and Proteomics

Subjects
Staphylococcus aureus, IgG/metabolism, Immunology, Receptors, IgG, Complement, Receptors, IgG/metabolism, Receptors, Complement, Phagocytosis, Staphylococcal Protein A/metabolism, Complement C1, Immunoglobulin G, Receptors, Immunology and Allergy, Humans, Staphylococcal Protein A, Immunoglobulin G/immunology
Abstract

IgG molecules are crucial for the human immune response against bacterial infections. IgGs can trigger phagocytosis by innate immune cells, like neutrophils. To do so, IgGs should bind to the bacterial surface via their variable Fab regions and interact with Fcγ receptors and complement C1 via the constant Fc domain. C1 binding to IgG-labeled bacteria activates the complement cascade, which results in bacterial decoration with C3-derived molecules that are recognized by complement receptors on neutrophils. Next to FcγRs and complement receptors on the membrane, neutrophils also express the intracellular neonatal Fc receptor (FcRn). We previously reported that staphylococcal protein A (SpA), a key immune-evasion protein of Staphylococcus aureus, potently blocks IgG-mediated complement activation and killing of S. aureus by interfering with IgG hexamer formation. SpA is also known to block IgG-mediated phagocytosis in absence of complement, but the mechanism behind it remains unclear. In this study, we demonstrate that SpA blocks IgG-mediated phagocytosis and killing of S. aureus and that it inhibits the interaction of IgGs with FcγRs (FcγRIIa and FcγRIIIb, but not FcγRI) and FcRn. Furthermore, our data show that multiple SpA domains are needed to effectively block IgG1-mediated phagocytosis. This provides a rationale for the fact that SpA from S. aureus contains four to five repeats. Taken together, our study elucidates the molecular mechanism by which SpA blocks IgG-mediated phagocytosis and supports the idea that in addition to FcγRs, the intracellular FcRn is also prevented from binding IgG by SpA.

Published
2022

27. Author response: Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae

Author

Aguinagalde Salazar, Leire, primary, den Boer, Maurits A, additional, Castenmiller, Suzanne M, additional, Zwarthoff, Seline A, additional, de Haas, Carla, additional, Aerts, Piet C, additional, Beurskens, Frank J, additional, Schuurman, Janine, additional, Heck, Albert JR, additional, van Kessel, Kok, additional, and Rooijakkers, Suzan HM, additional

Published
2022
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31. Monoclonal antibodies effectively potentiate complement activation and phagocytosis of Staphylococcus epidermidis in neonatal human plasma

Author

de Vor, Lisanne, primary, Beudeker, Coco R., additional, Flier, Anne, additional, Scheepmaker, Lisette M., additional, Aerts, Piet C., additional, Vijlbrief, Daniel C., additional, Bekker, Mireille N., additional, Beurskens, Frank J., additional, van Kessel, Kok P. M., additional, de Haas, Carla J. C., additional, Rooijakkers, Suzan H. M., additional, and van der Flier, Michiel, additional

Published
2022
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32. Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Author

de Vor, Lisanne (author), van Dijk, Bruce (author), van Kessel, Kok (author), Kavanaugh, Jeffrey S. (author), de Haas, Carla (author), Aerts, Piet C. (author), Ramakers, R.M. (author), Beekman, F.J. (author), Weinans, H.H. (author), de Vor, Lisanne (author), van Dijk, Bruce (author), van Kessel, Kok (author), Kavanaugh, Jeffrey S. (author), de Haas, Carla (author), Aerts, Piet C. (author), Ramakers, R.M. (author), Beekman, F.J. (author), and Weinans, H.H. (author)

Abstract

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo., RST/Technici Pool, RST/Biomedical Imaging, Biomechanical Engineering, Biomaterials & Tissue Biomechanics

Published
2022
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33. Toward Understanding How Staphylococcal Protein A Inhibits IgG-Mediated Phagocytosis

Author

Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Cruz, Ana Rita, Bentlage, Arthur E H, Blonk, Robin, de Haas, Carla J C, Aerts, Piet C, Scheepmaker, Lisette M, Bouwmeester, Inge G, Lux, Anja, van Strijp, Jos A G, Nimmerjahn, Falk, van Kessel, Kok P M, Vidarsson, Gestur, Rooijakkers, Suzan H M, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Cruz, Ana Rita, Bentlage, Arthur E H, Blonk, Robin, de Haas, Carla J C, Aerts, Piet C, Scheepmaker, Lisette M, Bouwmeester, Inge G, Lux, Anja, van Strijp, Jos A G, Nimmerjahn, Falk, van Kessel, Kok P M, Vidarsson, Gestur, and Rooijakkers, Suzan H M

Published
2022

34. Correction: Polymerization of C9 enhances bacterial cell envelope damage and killing by membrane attack complex pores

Author

MMB Research line 1, Infection & Immunity, MMB, Doorduijn, Dennis J., Heesterbeek, Dani A.C., Ruyken, Maartje, de Haas, Carla J.C., Stapels, Daphne A.C., Aerts, Piet C., Rooijakkers, Suzan H.M., Bardoel, Bart W., MMB Research line 1, Infection & Immunity, MMB, Doorduijn, Dennis J., Heesterbeek, Dani A.C., Ruyken, Maartje, de Haas, Carla J.C., Stapels, Daphne A.C., Aerts, Piet C., Rooijakkers, Suzan H.M., and Bardoel, Bart W.

Published
2022

35. Monoclonal antibodies effectively potentiate complement activation and phagocytosis of Staphylococcus epidermidis in neonatal human plasma

Author

MMB Research line 1, Infection & Immunity, Infectieziekten onderzoek1 (Bont), MMB, MS Neonatologie, Child Health, MS Verloskunde, Circulatory Health, Infectieziekten patientenzorg, de Vor, Lisanne, Beudeker, Coco R., Flier, Anne, Scheepmaker, Lisette M., Aerts, Piet C., Vijlbrief, Daniel C., Bekker, Mireille N., Beurskens, Frank J., van Kessel, Kok P.M., de Haas, Carla J.C., Rooijakkers, Suzan H.M., van der Flier, Michiel, MMB Research line 1, Infection & Immunity, Infectieziekten onderzoek1 (Bont), MMB, MS Neonatologie, Child Health, MS Verloskunde, Circulatory Health, Infectieziekten patientenzorg, de Vor, Lisanne, Beudeker, Coco R., Flier, Anne, Scheepmaker, Lisette M., Aerts, Piet C., Vijlbrief, Daniel C., Bekker, Mireille N., Beurskens, Frank J., van Kessel, Kok P.M., de Haas, Carla J.C., Rooijakkers, Suzan H.M., and van der Flier, Michiel

Published
2022

36. Toward Understanding How Staphylococcal Protein A Inhibits IgG-Mediated Phagocytosis

Author

MMB, MMB Research line 1, Infection & Immunity, Cruz, Ana Rita, Bentlage, Arthur E H, Blonk, Robin, de Haas, Carla J C, Aerts, Piet C, Scheepmaker, Lisette M, Bouwmeester, Inge G, Lux, Anja, van Strijp, Jos A G, Nimmerjahn, Falk, van Kessel, Kok P M, Vidarsson, Gestur, Rooijakkers, Suzan H M, MMB, MMB Research line 1, Infection & Immunity, Cruz, Ana Rita, Bentlage, Arthur E H, Blonk, Robin, de Haas, Carla J C, Aerts, Piet C, Scheepmaker, Lisette M, Bouwmeester, Inge G, Lux, Anja, van Strijp, Jos A G, Nimmerjahn, Falk, van Kessel, Kok P M, Vidarsson, Gestur, and Rooijakkers, Suzan H M

Published
2022

37. Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Author

MMB Research line 1, Infection & Immunity, ORT Research, MMB, MMB Medische Staf, Radionuclide Apotheek, Translational Neuroscience, Researchgr. Nucleaire Geneeskunde, Cancer, MS Orthopaedie Algemeen, Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, de Vor, Lisanne, van Dijk, Bruce, van Kessel, Kok, Kavanaugh, Jeffrey S., de Haas, Carla, Aerts, Piet C., Viveen, Marco C., Boel, Edwin C., Fluit, Ad C., Kwiecinski, Jakub M., Krijger, Gerard C., Ramakers, Ruud M., Beekman, Freek J., Dadachova, Ekaterina, Lam, Marnix G. E. H., Vogely, H. Charles, van der Wal, Bart C. H., van Strijp, Jos A. G., Horswill, Alexander R., Weinans, Harrie, Rooijakkers, Suzan H. M., MMB Research line 1, Infection & Immunity, ORT Research, MMB, MMB Medische Staf, Radionuclide Apotheek, Translational Neuroscience, Researchgr. Nucleaire Geneeskunde, Cancer, MS Orthopaedie Algemeen, Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, de Vor, Lisanne, van Dijk, Bruce, van Kessel, Kok, Kavanaugh, Jeffrey S., de Haas, Carla, Aerts, Piet C., Viveen, Marco C., Boel, Edwin C., Fluit, Ad C., Kwiecinski, Jakub M., Krijger, Gerard C., Ramakers, Ruud M., Beekman, Freek J., Dadachova, Ekaterina, Lam, Marnix G. E. H., Vogely, H. Charles, van der Wal, Bart C. H., van Strijp, Jos A. G., Horswill, Alexander R., Weinans, Harrie, and Rooijakkers, Suzan H. M.

Published
2022

39. Polymerization of C9 enhances bacterial cell envelope damage and killing by membrane attack complex pores

Author

Doorduijn, Dennis J., Meri, Seppo, Heesterbeek, Dani A. C., Ruyken, Maartje, Haas, Carla J. C. de, Stapels, Daphne A. C., Aerts, Piet C., Rooijakkers, Suzan H. M., Bardoel, Bart W., and Infectiebiologie

Abstract

Complement proteins can form membrane attack complex (MAC) pores that directly kill Gram-negative bacteria. MAC pores assemble by stepwise binding of C5b, C6, C7, C8 and finally C9, which can polymerize into a transmembrane ring of up to 18 C9 monomers. It is still unclear if the assembly of a polymeric-C9 ring is necessary to sufficiently damage the bacterial cell envelope to kill bacteria. In this paper, polymerization of C9 was prevented without affecting binding of C9 to C5b-8, by locking the first transmembrane helix domain of C9. Using this system, we show that polymerization of C9 strongly enhanced damage to both the bacterial outer and inner membrane, resulting in more rapid killing of several Escherichia coli and Klebsiella strains in serum. By comparing binding of wildtype and ‘locked’ C9 by flow cytometry, we also show that polymerization of C9 is impaired when the amount of available C9 per C5b-8 is limited. This suggests that an excess of C9 is required to efficiently form polymeric-C9. Finally, we show that polymerization of C9 was impaired on complement-resistant E. coli strains that survive killing by MAC pores. This suggests that these bacteria can specifically block polymerization of C9. All tested complement-resistant E. coli expressed LPS O-antigen (O-Ag), compared to only one out of four complement-sensitive E. coli. By restoring O-Ag expression in an O-Ag negative strain, we show that the O-Ag impairs polymerization of C9 and results in complement-resistance. Altogether, these insights are important to understand how MAC pores kill bacteria and how bacterial pathogens can resist MAC-dependent killing.

Published
2021

41. Staphylococcal protein A inhibits IgG-mediated phagocytosis by blocking the interaction of IgGs with FcγRs and FcRn

Author

Cruz, Ana Rita, primary, Bentlage, Arthur E. H., additional, Blonk, Robin, additional, de Haas, Carla J. C., additional, Aerts, Piet C., additional, Scheepmaker, Lisette M., additional, Bouwmeester, Inge G., additional, Lux, Anja, additional, van Strijp, Jos A. G., additional, Nimmerjahn, Falk, additional, van Kessel, Kok P. M., additional, Vidarsson, Gestur, additional, and Rooijakkers, Suzan H. M., additional

Published
2022
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42. Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae

Author

Aguinagalde, Leire, primary, den Boer, Maurits A., additional, Castenmiller, Suzanne M., additional, Zwarthoff, Seline A., additional, Gosselaar-de Haas, Carla J.C, additional, Aerts, Piet C., additional, Beurskens, Frank J., additional, Schuurman, Janine, additional, Heck, Albert J.R., additional, van Kessel, Kok P.M., additional, and Rooijakkers, Suzan H.M., additional

Published
2022
Full Text
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43. Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Author

de Vor, Lisanne, primary, van Dijk, Bruce, primary, van Kessel, Kok, additional, Kavanaugh, Jeffrey S, additional, de Haas, Carla, additional, Aerts, Piet C, additional, Viveen, Marco C, additional, Boel, Edwin C, additional, Fluit, Ad C, additional, Kwiecinski, Jakub M, additional, Krijger, Gerard C, additional, Ramakers, Ruud M, additional, Beekman, Freek J, additional, Dadachova, Ekaterina, additional, Lam, Marnix GEH, additional, Vogely, H Charles, additional, van der Wal, Bart CH, additional, van Strijp, Jos AG, additional, Horswill, Alexander R, additional, Weinans, Harrie, additional, and Rooijakkers, Suzan HM, additional

Published
2022
Full Text
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44. Author response: Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Author

de Vor, Lisanne, primary, van Dijk, Bruce, primary, van Kessel, Kok, additional, Kavanaugh, Jeffrey S, additional, de Haas, Carla, additional, Aerts, Piet C, additional, Viveen, Marco C, additional, Boel, Edwin C, additional, Fluit, Ad C, additional, Kwiecinski, Jakub M, additional, Krijger, Gerard C, additional, Ramakers, Ruud M, additional, Beekman, Freek J, additional, Dadachova, Ekaterina, additional, Lam, Marnix GEH, additional, Vogely, H Charles, additional, van der Wal, Bart CH, additional, van Strijp, Jos AG, additional, Horswill, Alexander R, additional, Weinans, Harrie, additional, and Rooijakkers, Suzan HM, additional

Published
2021
Full Text
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47. The Orphan Immune Receptor LILRB3 Modulates Fc Receptor-Mediated Functions of Neutrophils

Author

Zhao, Yuxi, van Woudenbergh, Esther, Zhu, Jing, Heck, Albert J R, van Kessel, Kok P M, de Haas, Carla J C, Aerts, Piet C, van Strijp, Jos A G, McCarthy, Alex J, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., and Biomolecular Mass Spectrometry and Proteomics

Subjects
Receptors, Fc/metabolism, Receptors, Immunologic/genetics, Neutrophils/immunology, Primary Cell Culture, Antigens, CD/genetics, Cell Differentiation/immunology, Neutrophil Activation, Staphylococcal Infections/immunology, Cell Line, Phagocytosis, Reactive Oxygen Species/metabolism, Humans, Recombinant Proteins/genetics, Down-Regulation/immunology, Staphylococcus capitis/immunology
Abstract

Neutrophils are critical to the generation of effective immune responses and for killing invading microbes. Paired immune receptors provide important mechanisms to modulate neutrophil activation thresholds and effector functions. Expression of the leukocyte Ig-like receptor (LILR)A6 (ILT8/CD85b) and LILRB3 (ILT5/CD85a) paired-receptor system on human neutrophils has remained unclear because of the lack of specific molecular tools. Additionally, there is little known of their possible functions in neutrophil biology. The objective of this study was to characterize expression of LILRA6/LILRB3 receptors during human neutrophil differentiation and activation, and to assess their roles in modulating Fc receptor-mediated effector functions. LILRB3, but not LILRA6, was detected in human neutrophil lysates following immunoprecipitation by mass spectrometry. We demonstrate high LILRB3 expression on the surface of resting neutrophils and release from the surface following neutrophil activation. Surface expression was recapitulated in a human PLB-985 cell model of neutrophil-like differentiation. Continuous ligation of LILRB3 inhibited key IgA-mediated effector functions, including production of reactive oxygen species, phagocytic uptake, and microbial killing. This suggests that LILRB3 provides an important checkpoint to control human neutrophil activation and their antimicrobial effector functions during resting and early-activation stages of the neutrophil life cycle.

Published
2020

48. Polymerization of C9 enhances bacterial cell envelope damage and killing by membrane attack complex pores

Author

Meri, Seppo, Doorduijn, Dennis J., Heesterbeek, Dani A. C., Ruyken, Maartje, Haas, Carla J. C. de, Stapels, Daphne A. C., Aerts, Piet C., Rooijakkers, Suzan H. M., Bardoel, Bart W., Meri, Seppo, Doorduijn, Dennis J., Heesterbeek, Dani A. C., Ruyken, Maartje, Haas, Carla J. C. de, Stapels, Daphne A. C., Aerts, Piet C., Rooijakkers, Suzan H. M., and Bardoel, Bart W.

Abstract

Complement proteins can form membrane attack complex (MAC) pores that directly kill Gram-negative bacteria. MAC pores assemble by stepwise binding of C5b, C6, C7, C8 and finally C9, which can polymerize into a transmembrane ring of up to 18 C9 monomers. It is still unclear if the assembly of a polymeric-C9 ring is necessary to sufficiently damage the bacterial cell envelope to kill bacteria. In this paper, polymerization of C9 was prevented without affecting binding of C9 to C5b-8, by locking the first transmembrane helix domain of C9. Using this system, we show that polymerization of C9 strongly enhanced damage to both the bacterial outer and inner membrane, resulting in more rapid killing of several Escherichia coli and Klebsiella strains in serum. By comparing binding of wildtype and ‘locked’ C9 by flow cytometry, we also show that polymerization of C9 is impaired when the amount of available C9 per C5b-8 is limited. This suggests that an excess of C9 is required to efficiently form polymeric-C9. Finally, we show that polymerization of C9 was impaired on complement-resistant E. coli strains that survive killing by MAC pores. This suggests that these bacteria can specifically block polymerization of C9. All tested complement-resistant E. coli expressed LPS O-antigen (O-Ag), compared to only one out of four complement-sensitive E. coli. By restoring O-Ag expression in an O-Ag negative strain, we show that the O-Ag impairs polymerization of C9 and results in complement-resistance. Altogether, these insights are important to understand how MAC pores kill bacteria and how bacterial pathogens can resist MAC-dependent killing.

Published
2021

49. C1q binding to surface-bound IgG is stabilized by C1r2s2 proteases

Author

Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Zwarthoff, Seline A., Widmer, Kevin, Kuipers, Annemarie, Strasser, Jürgen, Ruyken, Maartje, Aerts, Piet C., Haas, Carla J. C. de, Ugurlar, Deniz, Boer, Maurits A. den, Vidarsson, Gestur, Strijp, Jos A. G. van, Gros, Piet, Parren, Paul W. H. I., Kessel, Kok P. M. van, Preiner, Johannes, Beurskens, Frank J., Schuurman, Janine, Ricklin, Daniel, Rooijakkers, Suzan H. M., Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Zwarthoff, Seline A., Widmer, Kevin, Kuipers, Annemarie, Strasser, Jürgen, Ruyken, Maartje, Aerts, Piet C., Haas, Carla J. C. de, Ugurlar, Deniz, Boer, Maurits A. den, Vidarsson, Gestur, Strijp, Jos A. G. van, Gros, Piet, Parren, Paul W. H. I., Kessel, Kok P. M. van, Preiner, Johannes, Beurskens, Frank J., Schuurman, Janine, Ricklin, Daniel, and Rooijakkers, Suzan H. M.

Published
2021

50. Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation

Author

Sub Biomol.Mass Spectrometry & Proteom., Dep Scheikunde, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Cruz, Ana Rita, Boer, Maurits A den, Strasser, Jürgen, Zwarthoff, Seline A, Beurskens, Frank J, de Haas, Carla J C, Aerts, Piet C, Wang, Guanbo, de Jong, Rob N, Bagnoli, Fabio, van Strijp, Jos A G, van Kessel, Kok P M, Schuurman, Janine, Preiner, Johannes, Heck, Albert J R, Rooijakkers, Suzan H M, Sub Biomol.Mass Spectrometry & Proteom., Dep Scheikunde, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Cruz, Ana Rita, Boer, Maurits A den, Strasser, Jürgen, Zwarthoff, Seline A, Beurskens, Frank J, de Haas, Carla J C, Aerts, Piet C, Wang, Guanbo, de Jong, Rob N, Bagnoli, Fabio, van Strijp, Jos A G, van Kessel, Kok P M, Schuurman, Janine, Preiner, Johannes, Heck, Albert J R, and Rooijakkers, Suzan H M

Published
2021

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