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Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia

2018Journal article Restricted access
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dc.contributor.authorErcoli, Giuseppe
dc.contributor.authorFernandes, Vitor E.
dc.contributor.authorChung, Wen Y.
dc.contributor.authorWanford, Joseph J.
dc.contributor.authorThomson, Sarah
dc.contributor.authorBayliss, Christopher D.
dc.contributor.authorStraatman, Kornelis
dc.contributor.authorCrocker, Paul R.
dc.contributor.authorDennison, Ashley
dc.contributor.authorMartinez-Pomares, Luisa
dc.contributor.authorAndrew, Peter W.
dc.contributor.authorMoxon, E. Richard
dc.contributor.authorOggioni, Marco R.
dc.date.accessioned2018-04-24T15:08:44Z
dc.date.available2018-04-24T15:08:44Z
dc.date.issued2018
dc.description.abstractBacterial septicaemia is a major cause of mortality, but its pathogenesis remains poorly understood. In experimental pneumococcal murine intravenous infection, an initial reduction of bacteria in the blood is followed hours later by a fatal septicaemia. These events represent a population bottleneck driven by efficient clearance of pneumococci by splenic macrophages and neutrophils, but as we show in this study, accompanied by occasional intracellular replication of bacteria that are taken up by a subset of CD169+ splenic macrophages. In this model, proliferation of these sequestered bacteria provides a reservoir for dissemination of pneumococci into the bloodstream, as demonstrated by its prevention using an anti-CD169 monoclonal antibody treatment. Intracellular replication of pneumococci within CD169+ splenic macrophages was also observed in an ex vivo porcine spleen, where the microanatomy is comparable with humans. We also showed that macrolides, which effectively penetrate macrophages, prevented septicaemia, whereas beta-lactams, with inefficient intracellular penetration, failed to prevent dissemination to the blood. Our findings define a shift in our understanding of the pneumococcus from an exclusively extracellular pathogen to one with an intracellular phase. These findings open the door to the development of treatments that target this early, previously unrecognized intracellular phase of bacterial sepsis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/s41564-018-0147-1pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/10654
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNaturept_PT
dc.subjectBacterial infectionpt_PT
dc.subjectBacterial pathogenesispt_PT
dc.subjectInfectionpt_PT
dc.subjectPathogenspt_PT
dc.titleIntracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage610pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage600pt_PT
oaire.citation.titleNature Microbiologypt_PT
oaire.citation.volume3pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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