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dc.contributor.authorCuypers, Fabian
dc.contributor.authorKlabunde, Björn
dc.contributor.authorGesell Salazar, Manuela
dc.contributor.authorSurabhi, Surabhi
dc.contributor.authorSkorka, Sebastian B
dc.contributor.authorBurchhardt, Gerhard
dc.contributor.authorMichalik, Stephan
dc.contributor.authorThiele, Thomas
dc.contributor.authorRohde, Manfred
dc.contributor.authorVölker, Uwe
dc.contributor.authorHammerschmidt, Sven
dc.contributor.authorSiemens, Nikolai
dc.date.accessioned2020-06-08T13:43:25Z
dc.date.available2020-06-08T13:43:25Z
dc.date.issued2020-05-23
dc.identifier.citationJ Infect Dis. 2020;jiaa277. doi:10.1093/infdis/jiaa277.en_US
dc.identifier.pmid32445565
dc.identifier.doi10.1093/infdis/jiaa277
dc.identifier.urihttp://hdl.handle.net/10033/622284
dc.description.abstractBackground: In tissue infections, adenosine triphosphate (ATP) is released into extracellular space and contributes to purinergic chemotaxis. Neutrophils are important players in bacterial clearance and recruited to the site of tissue infections. Pneumococcal infections can lead to uncontrolled hyper-inflammation of the tissue along with substantial tissue damage through excessive neutrophil activation and uncontrolled granule release. We aimed to investigate the role of ATP in neutrophil response to pneumococcal infections. Methods: Primary human neutrophils were exposed to the pneumococcal strain TIGR4 and its pneumolysin deficient mutant or directly to different concentrations of recombinant pneumolysin. Neutrophil activation was assessed by measurement of secreted azurophilic granule protein resistin and profiling of the secretome, using mass spectrometry. Results: Pneumococci are potent inducers of neutrophil degranulation. Pneumolysin was identified as a major trigger of neutrophil activation. This process is partially lysis independent and inhibited by ATP. Pneumolysin and ATP interact with each other in the extracellular space leading to reduced neutrophil activation. Proteome analyses of the neutrophil secretome confirmed that ATP inhibits pneumolysin-dependent neutrophil activation. Conclusions: Our findings suggest that despite its cytolytic activity, pneumolysin serves as a potent neutrophil activating factor. Extracellular ATP mitigates pneumolysin induced neutrophil activation.en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectStreptococcus pneumoniaeen_US
dc.subjectATPen_US
dc.subjectdegranulationen_US
dc.subjectneutrophilsen_US
dc.subjectpneumolysinen_US
dc.titleAdenosine Triphosphate Neutralizes Pneumolysin-induced Neutrophil Activation.en_US
dc.typeArticleen_US
dc.identifier.eissn1537-6613
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalThe Journal of infectious diseasesen_US
dc.source.journaltitleThe Journal of infectious diseases
dc.source.countryUnited States


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