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Pneumococci cause meningitis by invading the blood and penetrating the blood\u2013brain 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.<\/jats:p>","DOI":"10.1084\/jem.20161668","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T14:10:22Z","timestamp":1495030222000},"page":"1619-1630","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":112,"title":["pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion"],"prefix":"10.1084","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-9120","authenticated-orcid":true,"given":"Federico","family":"Iovino","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden 1"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Yeon","family":"Engelen-Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, Netherlands 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, Netherlands 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik","family":"van de Beek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, Netherlands 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"van der Ende","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, Netherlands 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merche","family":"Valls Seron","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, Netherlands 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mellroth","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden 1"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Muschiol","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden 1"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bergstrand","sequence":"additional","affiliation":[{"name":"Department of Applied Physics, KTH Royal Institute of Technology, SE-114 28 Stockholm, Sweden 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerker","family":"Widengren","sequence":"additional","affiliation":[{"name":"Department of Applied Physics, KTH Royal Institute of Technology, SE-114 28 Stockholm, Sweden 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-4759","authenticated-orcid":true,"given":"Birgitta","family":"Henriques-Normark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden 1"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden 2"},{"name":"Lee Kong Chian School of Medicine (LKC), Nanyang Technological University, Singapore 639798, Singapore 4"},{"name":"Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 639798, Singapore 5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,5,17]]},"reference":[{"key":"2023072603551639600_bib1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2013brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. 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