Staphylococcus aureus bound to complement receptor 1 on human erythrocytes by bispecific monoclonal antibodies is phagocytosed by acceptor macrophages

Immunology Letters
Edit GyimesiR P Taylor

Abstract

Antibiotic resistant strains of Staphylococcus aureus pose a growing threat to public health, and immunotherapy offers potential modalities to combat antibiotic resistance. We prepared bispecific monoclonal antibody complexes (heteropolymers, HP), specific for the primate erythrocyte complement C3b receptor (CR1) and type 5 capsular polysaccharide of the T5 isolate of S. aureus. Fluorescence microscopy and flow cytometry revealed that HP promote binding of S. aureus to human erythrocytes. Incubation of erythrocyte-bound, HP-opsonized S. aureus with human monocyte/macrophages or mouse macrophage cell lines led to transfer, internalization and killing of bacteria by macrophages with little erythrocyte loss. This reaction is similar to the process in which C3b-opsonized substrates, bound to erythrocyte CR1 by immune adherence, are transferred to acceptor phagocytes. Our results provide the basis for development of an in vivo paradigm focused on immunotherapeutic approaches for treatment of infections due to antibiotic resistant bacteria.

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Citations

Dec 20, 2012·Journal of Pediatric Hematology/oncology·Ami BallinMona Boaz
Mar 3, 2010·Expert Opinion on Drug Delivery·Vladimir R Muzykantov
Jun 10, 2010·Expert Opinion on Biological Therapy·Michael Otto
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Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul V BeumRonald P Taylor
Jul 12, 2018·Nature Communications·Jacob S BrennerVladimir Muzykantov
Feb 6, 2021·Frontiers in Immunology·Grace R PidwillSimon J Foster

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