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

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.

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

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

Av författaren/redakt...: Iovino, Federico; Engelen-Lee, Joo ...; Brouwer, Matthij ...; van de Beek, Die ...; van der Ende, Ar ...; Seron, Merche Va ...; visa fler...; Mellroth, Peter; Muschiol, Sandra; Bergstrand, Jan; Widengren, Jerke ...; Henriques-Normar ...; visa färre...

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