Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81456
Title: pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
Authors: Iovino, Federico
Engelen-Lee, Joo-Yeon
Brouwer, Matthijs
van de Beek, Diederik
van der Ende, Arie
Valls Seron, Merche
Mellroth, Peter
Muschiol, Sandra
Bergstrand, Jan
Widengren, Jerker
Henriques-Normark, Birgitta
Keywords: Pneumococcal adhesins
Bacterial meningitis
Issue Date: 2017
Source: Iovino, F., Engelen-Lee, J.-Y., Brouwer, M., van de Beek, D., van der Ende, A., Valls Seron, M., et al. (2017). pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion. The Journal of Experimental Medicine, 214(6), 1619-1630.
Series/Report no.: The Journal of Experimental Medicine
Abstract: 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.
URI: https://hdl.handle.net/10356/81456
http://hdl.handle.net/10220/43471
ISSN: 0022-1007
DOI: 10.1084/jem.20161668
Rights: © 2017 The Author(s) (published by Rockefeller University Press (RUP)). This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
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