title: Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes.
abstract: Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3 h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1β and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.
authors.affiliation: Oral Microbiology and Immunology, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Plattenstrasse 11, 8032 Zürich, Switzerland. george.belibasakis@zzm.uzh.ch
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000382:microbiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011419:Propidium / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C468563:NLRP6 protein, human; C402202:PYCARD protein, human; D011419:Propidium; D007770:L-Lactate Dehydrogenase; D020170:Caspase 1