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Sökning: L773:1754 8403 > Modelling staphyloc...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003618naa a2200385 4500
001oai:prod.swepub.kib.ki.se:132332367
003SwePub
008240811s2015 | |||||||||||000 ||eng|
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1323323672 URI
0247 a https://doi.org/10.1242/dmm.0219232 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Shambat, SMu Karolinska Institutet4 aut
2451 0a Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology
264 1b The Company of Biologists,c 2015
520 a Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, but yet the tissue destructive events remain elusive partly due to lack of mechanistic studies in human lung tissue. In this study, a 3D tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and PVL, and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin in the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified by toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils, and a combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for studies of staphylococcal pneumonia in a human setting, and the results revealed that a combination and levels of α-toxin and PVL correlate with tissue pathology and clinical outcome associated with pneumonia.
7001 a Chen, PR4 aut
7001 a Hoang, ATN4 aut
7001 a Bergsten, Hu Karolinska Institutet4 aut
7001 a Vandenesch, F4 aut
7001 a Siemens, Nu Karolinska Institutet4 aut
7001 a Lina, G4 aut
7001 a Monk, IR4 aut
7001 a Foster, TJ4 aut
7001 a Arakere, G4 aut
7001 a Svensson, Mu Karolinska Institutet4 aut
7001 a Norrby-Teglund, Au Karolinska Institutet4 aut
7102 a Karolinska Institutet4 org
7730 t Disease models & mechanismsd : The Company of Biologistsg 8:11, s. 1413-1425q 8:11<1413-1425x 1754-8411x 1754-8403
8564 u http://dmm.biologists.org/content/8/11/1413.full.pdf
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:132332367
8564 8u https://doi.org/10.1242/dmm.021923

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