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pIgR and PEC AM-1 b...
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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 ...
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2017-05-17
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Rockefeller University Press,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-210488
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-210488URI
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https://doi.org/10.1084/jem.20161668DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:135991680URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20170705
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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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Engelen-Lee, Joo-Yeon
(author)
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Brouwer, Matthijs
(author)
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van de Beek, Diederik
(author)
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van der Ende, Arie
(author)
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Seron, Merche Valls
(author)
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Mellroth, PeterKarolinska Institutet
(author)
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Muschiol, SandraKarolinska Institutet
(author)
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Bergstrand, JanKTH,Experimentell biomolekylär fysik(Swepub:kth)u1xi97g1
(author)
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Widengren, JerkerKTH,Experimentell biomolekylär fysik(Swepub:kth)u1i3g09c
(author)
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Henriques-Normark, BirgittaKarolinska Institutet
(author)
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Karolinska InstitutetExperimentell biomolekylär fysik
(creator_code:org_t)
Related titles
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In:Journal of Experimental Medicine: Rockefeller University Press214:6, s. 1619-16300022-10071540-9538
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Iovino, Federico
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Engelen-Lee, Joo ...
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Brouwer, Matthij ...
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van de Beek, Die ...
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van der Ende, Ar ...
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Seron, Merche Va ...
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Mellroth, Peter
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Muschiol, Sandra
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Bergstrand, Jan
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Widengren, Jerke ...
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Henriques-Normar ...
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- MEDICAL AND HEALTH SCIENCES
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Royal Institute of Technology
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Karolinska Institutet