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Staphylococcus aureus-mediated caspase-1 activation in human neutrophils: a role for Panton-Valentine Leukocidin?
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Rocky Mountins Laboratories, National Institute an Infectious Deseases, National Institute of Health, 903 South 4th St, Hamilton, Mt 59840 USA.
Örebro University, School of Medicine, Örebro University, Sweden.ORCID iD: 0000-0001-5939-2932
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
(English)Manuscript (preprint) (Other academic)
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-30115OAI: oai:DiVA.org:oru-30115DiVA, id: diva2:638823
Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Inflammasomes: defense guardians in host-microbe defence
Open this publication in new window or tab >>Inflammasomes: defense guardians in host-microbe defence
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The inflammasomes are emerging as key regulators of the innate immune response as they response to cellular infection, tissue damage and/or stress. Activated inflammasomes provide a signalling platform for caspase-1 activation which subsequently processes the maturation of interleukin (IL)-1β and IL-18, and in addition promotes cell death, named pyroptosis. These effector mechanisms of the inflammasome constitute an important part of the innate immune response in host-defence.

The aims of this thesis were to elucidate if the inflammasome is activated by specific pathogens, and if genetic variations lead to susceptibility to severe inflammatory diseases, such as blood stream infections. We found that the commensal pathogens Staphylococcus aureus and Propionibacterium acnes induce caspase-1 activation, the latter being a stronger activator. The data also propose that it is rather the bacterial ligands than the secreted toxins of P. acnes that induce inflammasome activation. Even though the S. aureus PVL-toxin induces a caspase-1 activation, involvement of other virulence factors are of importance. Upon S. aureus and P. acnes stimulation, inter-individual variations were found, implying that the characteristics of the host innate immune system, rather than the properties of the bacteria, are decisive for the inflammatory response. Indeed, healthy individuals with the combined polymorphisms of the NLRP3 inflammasome (C10X/Q705K) have higher levels of spontaneous IL-1β, and most intriguingly C10X polymorphism showed a strong correlation with patients with bacteremia.

In conclusion, these studies suggest that different pathogens activate the inflammasomes to various degrees. The genetics of the host innate immune system, rather than the properties of the bacteria, define the inflammatory response against these bacteria, and specific genetic variations such as C10X polymorphism can increase the susceptibility for disease development.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 76
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 88
Keyword
Innate immunity, inflammasome, leukocytes, cytokines, Staphylococcus aureus, Propionibacterium acnes, inflammation, infection, gene variants, polymorphism.
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-28523 (URN)978-91-7668-923-3 (ISBN)
Public defence
2013-06-05, Wilandersalen, M-huset, Universitetetssjukhuset Örebro, Grev Rosen gatan 18, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-04-02 Created: 2013-04-02 Last updated: 2017-10-17Bibliographically approved

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CiteExportLink to record
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