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Propionibacterium acnes activates caspase-1 in human neutrophils
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.ORCID iD: 0000-0001-5939-2932
2013 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 7, p. 652-63Article in journal (Refereed) Published
Abstract [en]

Propionibacterium acnes is a Gram-positive, slow-growing, anaerobic bacillus, predominantly found as a commensal on the skin and mucous membranes of adults. It is, however, also considered an opportunistic pathogen; mostly associated with acne vulgaris, but rarely also with severe infections such as infective endocarditis, prosthetic joint infections, and deep sternal wound infections following cardiothoracic surgery. In addition, P. acnes has recently been found in high frequency in prostate tissue from patients with prostatitis and prostate cancer. The NOD-like receptors (NLR) act as intracellular sensors of microbial components, and a number of various bacteria have been found to induce assembling and activation of NLR-inflammasomes; leading to a pro-inflammatory response. The inflammasome-mediated formation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 involves the auto-proteolytic maturation of caspase-1. This study investigated if P. acnes activates inflammasomes. Propionibacterium acnes isolates (n = 29) with diverse origin were used as stimuli for peripheral leukocytes obtained from blood donors (BDs). The activity of inflammasomes was determined by measuring caspase-1 by flow cytometry and cytokine production by ELISA. A significant amount of caspase-1 was found in neutrophils upon P. acnes stimulation, whereas only a modest activation was seen in monocytes. The activation was mainly produced by components of the bacterial cell and no exo-products, because heat-killed and live bacteria caused high activation of caspase-1 as well as cytokine production, whereas the bacterial supernatant elicited minor effect. The response among different BDs varied significantly, almost fivefold. In addition, P. acnes of various origins showed considerable variation, however, the commensal isolates showed a stronger response compared with the invasive. In conclusion, although regarded as a harmless commensal of the skin, P. acnes strongly activates the inflammasome of human peripheral neutrophils.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2013. Vol. 121, no 7, p. 652-63
Keywords [en]
Propionibacterium acnes, anaerobic bacteria, innate immunity, inflammasome, leukocytes, prostate.
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-30113DOI: 10.1111/apm.12035ISI: 000320614200009PubMedID: 23278288Scopus ID: 2-s2.0-84879497934OAI: oai:DiVA.org:oru-30113DiVA, id: diva2:638817
Note

Funding Agencies:

Research Committee of the County Council of Orebro 

Nyckelfonden at Orebro University Hospital 

King Gustaf V Memorial Foundation 

Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2018-09-11Bibliographically 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
Keywords
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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Sahdo, BerollaSärndahl, EvaElgh, FredrikSöderquist, Bo

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