University of Leicester
Browse
Ercoli Nature Microbiology 2018 final author version.pdf (1.23 MB)

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

Download (1.23 MB)
journal contribution
posted on 2018-04-20, 14:45 authored by Marco R. Oggioni, Giuseppe Ercoli, Vitor E. Fernandes, Wen Y. Chung, Joseph J. Wanford, Sarah Thomson, Christopher D. Bayliss, Kornelis Straatman, Paul R. Crocker, Ashley Dennison, Luisa Martinez-Pomares, Peter W. Andrew, E. Richard Moxon
Bacterial 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.

History

Citation

Nature Microbiology, 2018

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Genetics and Genome Biology

Version

  • AM (Accepted Manuscript)

Published in

Nature Microbiology

Publisher

Nature Publishing Group

eissn

2058-5276

Acceptance date

2018-03-08

Copyright date

2018

Available date

2018-10-16

Publisher version

http://www.nature.com/articles/s41564-018-0147-1

Notes

The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Keywords

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC