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  • Iovino, FedericoKarolinska Institutet (author)

pIgR and PEC AM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-05-17
  • Rockefeller University Press,2017
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-210488
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-210488URI
  • https://doi.org/10.1084/jem.20161668DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135991680URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20170705
  • Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood-brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Engelen-Lee, Joo-Yeon (author)
  • Brouwer, Matthijs (author)
  • van de Beek, Diederik (author)
  • van der Ende, Arie (author)
  • Seron, Merche Valls (author)
  • Mellroth, PeterKarolinska Institutet (author)
  • Muschiol, SandraKarolinska Institutet (author)
  • Bergstrand, JanKTH,Experimentell biomolekylär fysik(Swepub:kth)u1xi97g1 (author)
  • Widengren, JerkerKTH,Experimentell biomolekylär fysik(Swepub:kth)u1i3g09c (author)
  • Henriques-Normark, BirgittaKarolinska Institutet (author)
  • Karolinska InstitutetExperimentell biomolekylär fysik (creator_code:org_t)

Related titles

  • In:Journal of Experimental Medicine: Rockefeller University Press214:6, s. 1619-16300022-10071540-9538

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