| pubmed-article:19001420 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C0038411 | lld:lifeskim |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C0024432 | lld:lifeskim |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C0033414 | lld:lifeskim |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C1654934 | lld:lifeskim |
| pubmed-article:19001420 | lifeskim:mentions | umls-concept:C0075301 | lld:lifeskim |
| pubmed-article:19001420 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:19001420 | pubmed:dateCreated | 2009-1-5 | lld:pubmed |
| pubmed-article:19001420 | pubmed:abstractText | Group A Streptococcus (GAS) is a leading human bacterial pathogen capable of producing invasive infections even in previously healthy individuals. As frontline components of host innate defense, macrophages play a key role in control and clearance of GAS infections. We find GAS induces rapid, dose-dependent apoptosis of primary and cultured macrophages and neutrophils. The cell death pathway involves apoptotic caspases, is partly dependent on caspase-1, and requires GAS internalization by the phagocyte. Analysis of GAS virulence factor mutants, heterologous expression, and purified toxin studies identified the pore-forming cytolysin streptolysin O (SLO) as necessary and sufficient for the apoptosis-inducing phenotype. SLO-deficient GAS mutants induced less macrophage apoptosis in vitro and in vivo, allowed macrophage cytokine secretion, and were less virulent in a murine systemic infection model. Ultrastructural evidence of mitochondrial membrane remodeling, coupled with loss of mitochondrial depolarization and cytochrome c release, suggests a direct attack of the toxin initiates the intrinsic apoptosis pathway. A general caspase inhibitor blocked SLO-induced apoptosis and enhanced macrophage killing of GAS. We conclude that accelerated, caspase-dependent macrophage apoptosis induced by the pore-forming cytolysin SLO contributes to GAS immune evasion and virulence. | lld:pubmed |
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| pubmed-article:19001420 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19001420 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19001420 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19001420 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19001420 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19001420 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:19001420 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:HsuLi-ChungLC | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:NizetVictorV | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:KarinMichaelM | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:SalvesenGuy... | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:FreyTerrence... | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:TimmerAnjuli... | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:PenceMorgan... | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:TimmerJohn... | lld:pubmed |
| pubmed-article:19001420 | pubmed:author | pubmed-author:GhochaniMaria... | lld:pubmed |
| pubmed-article:19001420 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:19001420 | pubmed:day | 9 | lld:pubmed |
| pubmed-article:19001420 | pubmed:volume | 284 | lld:pubmed |
| pubmed-article:19001420 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19001420 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19001420 | pubmed:pagination | 862-71 | lld:pubmed |
| pubmed-article:19001420 | pubmed:dateRevised | 2010-9-23 | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:meshHeading | pubmed-meshheading:19001420... | lld:pubmed |
| pubmed-article:19001420 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19001420 | pubmed:articleTitle | Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis. | lld:pubmed |
| pubmed-article:19001420 | pubmed:affiliation | Department of Pediatrics, Biomedical Sciences Graduate Program, Laboratory of Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA. | lld:pubmed |
| pubmed-article:19001420 | pubmed:publicationType | Journal Article | lld:pubmed |
