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dc.contributor.authorCodemo, Marioen
dc.contributor.authorMuschiol, Sandraen
dc.contributor.authorIovino, Federicoen
dc.contributor.authorNannapaneni, Priyankaen
dc.contributor.authorPlant, Lauraen
dc.contributor.authorWai, Sun Nyunten
dc.contributor.authorHenriques-Normark, Birgittaen
dc.contributor.editorRappuoli, Rinoen
dc.identifier.citationCodemo, M., Muschiol, S., Iovino, F., Nannapaneni, P., Plant, L., Wai, S. N., & Henriques-Normark, B. (2018). Immunomodulatory effects of pneumococcal extracellular vesicles on cellular and humoral host defenses. mBio, 9(2), e00559-18-. doi:10.1128/mBio.00559-18en
dc.description.abstractGram-positive bacteria, including the major respiratory pathogen Streptococcus pneumoniae, were recently shown to produce extracellular vesicles (EVs) that likely originate from the plasma membrane and are released into the extracellular environment. EVs may function as cargo for many bacterial proteins, however, their involvement in cellular processes and their interactions with the innate immune system are poorly understood. Here, EVs from pneumococci were characterized and their immunomodulatory effects investigated. Pneumococcal EVs were protruding from the bacterial surface and released into the medium as 25 to 250 nm lipid stained vesicles containing a large number of cytosolic, membrane, and surface-associated proteins. The cytosolic pore-forming toxin pneumolysin was significantly enriched in EVs compared to a total bacterial lysate but was not required for EV formation. Pneumococcal EVs were internalized into A549 lung epithelial cells and human monocyte-derived dendritic cells and induced proinflammatory cytokine responses irrespective of pneumolysin content. EVs from encapsulated pneumococci were recognized by serum proteins, resulting in C3b deposition and formation of C5b-9 membrane attack complexes as well as factor H recruitment, depending on the presence of the choline binding protein PspC. Addition of EVs to human serum decreased opsonophagocytic killing of encapsulated pneumococci. Our data suggest that EVs may act in an immunomodulatory manner by allowing delivery of vesicle-associated proteins and other macromolecules into host cells. In addition, EVs expose targets for complement factors in serum, promoting pneumococcal evasion of humoral host defense.en
dc.format.extent15 p.en
dc.rights© 2018 Codemo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.subjectCellular and Humoral Defenseen
dc.subjectStreptococcus Pneumoniaeen
dc.titleImmunomodulatory effects of pneumococcal extracellular vesicles on cellular and humoral host defensesen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.contributor.researchSingapore Centre for Environmental Life Sciences and Engineeringen
dc.description.versionPublished versionen
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