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Cellular and molecular response of human macrophages exposed to Aggregatibacter actinomycetemcomitans leukotoxin.
Umeå University, Faculty of Medicine, Department of Odontology.
Umeå University, Faculty of Medicine, Department of Odontology.
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2011 (English)In: Cell death & disease, ISSN 2041-4889, Vol. 2, e126- p.Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter (Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative bacterium associated with severe forms of periodontitis. A leukotoxin, which belongs to the repeats-in-toxin family, is believed to be one of its virulence factors and to have an important role in the bacterium's pathogenicity. This toxin selectively kills human leukocytes by inducing apoptosis and lysis. Here, we report that leukotoxin-induced cell death of macrophages proceeded through a process that differs from the classical characteristics of apoptosis and necrosis. A. actinomycetemcomitans leukotoxin-induced several cellular and molecular mechanisms in human macrophages that led to a specific and excessive pro-inflammatory response with particular secretion of both interleukin (IL)-1β and IL-18. In addition, this pro-inflammatory cell death was inhibited by oxidized ATP, which indicates involvement of the purinergic receptor P2X(7) in this process. This novel virulence mechanism of the leukotoxin may have an important role in the pathogenic potential of this bacterium and can be a target for future therapeutic agents.

Place, publisher, year, edition, pages
Nature Publishing Group , 2011. Vol. 2, e126- p.
Keyword [en]
A. actinomycetemcomitans, leukotoxin, macrophages, pro-inflammatory response, P2X7 receptor
URN: urn:nbn:se:umu:diva-40881DOI: 10.1038/cddis.2011.6PubMedID: 21390060OAI: diva2:404976
Available from: 2011-03-19 Created: 2011-03-11 Last updated: 2011-03-21Bibliographically approved

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Kelk, PeymanClaesson, RolfSjöstedt, AndersJohansson, Anders
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Department of OdontologyClinical Bacteriology

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