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Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteremia
Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences. (iRiSC - Inflammatory Response and Infection Susceptibility Centre)
InfectoGnostics Research Campus Jena, Jena, Germany.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Research Laboratory.
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2019 (English)In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421Article in journal (Refereed) Epub ahead of print
Abstract [en]

The inflammasome is a multiprotein complex that mediates caspase-1 activation with subsequent maturation of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. The present study therefore aimed to investigate NLRP3 inflammasome activity in 20 S. aureus bacteremia patients, by repeated measurement during the first week of bacteremia, compared with controls. Caspase-1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (Fluorescent Labelled Inhibitor of Caspase-1), while IL-1β and IL-18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, mRNA expression of NLRP3, CASP1 (pro-caspase-1) and IL1B (pro-IL-1β) was analyzed by qPCR. We found induced caspase-1 activity in innate immune cells with subsequent release of IL-18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial inter-individual variation in caspase-1 activity between S. aureus bacteremia patients. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in S. aureus bacteremia could provide support in the effort to optimize management and treatment of each individual patient.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2019.
Keywords [en]
Caspase-1, NLRP3, Staphylococcus aureus, sepsis
National Category
Immunology
Identifiers
URN: urn:nbn:se:oru:diva-75829DOI: 10.1111/1348-0421.12738ISI: 000490350100001PubMedID: 31403210OAI: oai:DiVA.org:oru-75829DiVA, id: diva2:1345248
Note

Funding Agencies:

Nyckelfonden in Region Örebro County, Sweden  

Region Örebro County's Research Committee, Sweden  

ALF research funding in Region Örebro County, Sweden  

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-11-15Bibliographically approved

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Asfaw Idosa, BerhaneBäckman, AndersSärndahl, EvaSöderquist, Bo

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Asfaw Idosa, BerhaneBäckman, AndersSärndahl, EvaSöderquist, Bo
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