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        Antibody-mediated phagocytosis of S.Aureus: A comparison between Neutrophils and Macrophages

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        Antibody mediated phagocytosis of S.Aureus_ ResearchReport_C.Passerini_0126365.pdf (1.693Mb)
        Publication date
        2023
        Author
        Passerini, Claudio
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        Summary
        Staphylococcus aureus is recognised as one of the most threatening gram-positive bacterium for human health. Its pathogenesis is associated with the emergence of antibiotic-resistant strains but also by the ability to evade the immune system recognition mechansims. Monoclonal antibody therapy is a valuable therapeutic alternative against S. aureus that could be used to enhance our host innate immune response, mainly mediated by neutrophils and macrophages. To date, no effective vaccination exists to reduce the prevalence of S. aureus infections. In this study, we investigated the potential of three monoclonal antibodies (mAbs) targeting staphylococcal cell wall structures to enhance phagocytosis by human neutrophils and monocyte-derived macrophages. The phagocytic abilities of the two immune cells were assessed both in suspension and adhesion assays, to reflect the different in vitro conditions in which neutrophils and macrophages are usually studied, respectively. Bacteria were opsonized with mAbs, in the presence or absence of complement, and then combined with cells. In suspension, we found that IgG3 mAbs induced greater phagocytosis by both immune cells compared to IgG1 mAbs. The limited phagocytosis induced by IgG1 mAb was mainly attributed to presence of staphylococcal protein A (SpA} and second immunoglobulin-binding protein (Sbi), as revealed by our assay with the knock-out strain. We observed that macrophages’ phagocytic ability was mainly mAb-dependent, while neutrophils phagocytosis was ameliorated by complement presence. Furthermore, we observed that in adhesion non-opsonic mechanisms were also involved in the phagocytosis of both cell types, as opposed to the assays in suspension. In conclusion, we showed that the selected mAbs can enhance phagocytosis by improving bacterial opsonisation. Next, future research should investigate the mAbs influence on the killing efficacy of immune cells and establish a strong basis for development of future vaccine strategies.
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        https://studenttheses.uu.nl/handle/20.500.12932/43793
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