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

The Journal of Experimental Medicine
Federico IovinoBirgitta Henriques-Normark

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.

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Citations

Nov 3, 2017·Current Opinion in Infectious Diseases·Jan P BewersdorfStephen L Leib
Aug 31, 2018·European Journal of Immunology·Christoph Konradt, Christopher A Hunter
Nov 15, 2018·International Journal of Molecular Sciences·Belinda YauLay Khoon Too
Oct 29, 2019·Cellular Microbiology·Loic Le GuennecSandrine Bourdoulous
Nov 2, 2019·International Journal of Molecular Sciences·Rosanna HeroldChristian Schwerk
Nov 7, 2019·The Journal of Clinical Investigation·Ulrike BinskerJeffrey N Weiser
Jul 29, 2019·Journal of Neuroinflammation·Lukas MuriStephen L Leib
Mar 31, 2018·Nature Reviews. Microbiology·Jeffrey N WeiserJames C Paton
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Apr 28, 2018·The Journal of Infectious Diseases·Federico IovinoBirgitta Henriques-Normark
Nov 24, 2020·Frontiers in Cellular and Infection Microbiology·Anjali Anil, Anirban Banerjee
Jan 20, 2021·The Journal of Clinical Investigation·Romain Deshayes de CambronneJulie Guignot
Oct 20, 2020·American Journal of Respiratory and Critical Care Medicine·Federico Iovino, Birgitta Henriques-Normark
Feb 27, 2021·Frontiers in Microbiology·Stefan Ness, Markus Hilleringmann
Mar 28, 2021·Journal of Applied Microbiology·P S Lannes-CostaP E Nagao
Mar 27, 2021·Current Opinion in Neurology·Emma C WallRobert S Heyderman
Jun 22, 2021·Frontiers in Cellular Neuroscience·Kristine FarmenFederico Iovino
Jul 3, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Kai ZhengQiushui He
Mar 1, 2019·Journal of Innate Immunity·Ulrike BinskerSven Hammerschmidt

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Methods Mentioned

BETA
super-resolution microscopy
biopsy
super-resolution
biopsies
Coimmunoprecipitation
immunoprecipitation
PCR
FCS
ion-exchange chromatography

Software Mentioned

Imspector
ImageJ
RGB Profile Plot
SoftWoRx

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