Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-9-3
pubmed:abstractText
Meningitis occurs when blood-borne pathogens cross the blood-brain barrier (BBB) in a complex interplay between endothelial cells and microbial gene products. We sought to understand the initial response of the BBB to the human meningeal pathogen group B Streptococcus (GBS) and the organism's major virulence factors, the exopolysaccharide capsule and the beta-hemolysin/cytolysin toxin (beta-h/c). Using oligonucleotide microarrays, we found that GBS infection of human brain microvascular endothelial cells (HBMEC) induced a highly specific and coordinate set of genes including IL-8, Groalpha, Grobeta, IL-6, GM-CSF, myeloid cell leukemia sequence-1 (Mcl-1), and ICAM-1, which act to orchestrate neutrophil recruitment, activation, and enhanced survival. Most strikingly, infection with a GBS strain lacking beta-h/c resulted in a marked reduction in expression of genes involved in the immune response, while the unencapsulated strain generally induced similar or greater expression levels for the same subset of genes. Cell-free bacterial supernatants containing beta-h/c activity induced IL-8 release, identifying this toxin as a principal provocative factor for BBB activation. These findings were further substantiated in vitro and in vivo. Neutrophil migration across polar HBMEC monolayers was stimulated by GBS and its beta-h/c through a process involving IL-8 and ICAM-1. In a murine model of hematogenous meningitis, mice infected with beta-h/c mutants exhibited lower mortality and decreased brain bacterial counts compared with mice infected with the corresponding WT GBS strains.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10090394, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10231855, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10470554, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10510082, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10931941, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-10950777, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11008113, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11136446, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11159983, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11294868, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11320214, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11390502, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11500388, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11553553, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11756992, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11807693, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11821235, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-11830671, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-12085320, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-12397015, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-12490448, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-1280481, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-1379006, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-1497093, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-3889248, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-6991426, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-7682708, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-7911447, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-8253345, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-8304236, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-8751934, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-8945544, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-9156338, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-9184127, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-9291317, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-9331818, http://linkedlifedata.com/resource/pubmed/commentcorrection/12952922-9393798
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
736-44
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis.
pubmed:affiliation
Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, California 92093-0672, USA. kdoran@ucsd.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't