Search: onr:"swepub:oai:DiVA.org:kth-210488" >
pIgR and PEC AM-1 b...
pIgR and PEC AM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
-
- Iovino, Federico (author)
- Karolinska Institutet
-
Engelen-Lee, Joo-Yeon (author)
-
Brouwer, Matthijs (author)
-
show more...
-
van de Beek, Diederik (author)
-
van der Ende, Arie (author)
-
Seron, Merche Valls (author)
-
- Mellroth, Peter (author)
- Karolinska Institutet
-
- Muschiol, Sandra (author)
- Karolinska Institutet
-
- Bergstrand, Jan (author)
- KTH,Experimentell biomolekylär fysik
-
- Widengren, Jerker (author)
- KTH,Experimentell biomolekylär fysik
-
- Henriques-Normark, Birgitta (author)
- Karolinska Institutet
-
show less...
-
(creator_code:org_t)
- 2017-05-17
- 2017
- English.
-
In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:6, s. 1619-1630
- Related links:
-
https://rupress.org/...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Iovino, Federico
-
Engelen-Lee, Joo ...
-
Brouwer, Matthij ...
-
van de Beek, Die ...
-
van der Ende, Ar ...
-
Seron, Merche Va ...
-
show more...
-
Mellroth, Peter
-
Muschiol, Sandra
-
Bergstrand, Jan
-
Widengren, Jerke ...
-
Henriques-Normar ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
- Articles in the publication
-
Journal of Exper ...
- By the university
-
Royal Institute of Technology
-
Karolinska Institutet