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Role of Aggregatibacter actinomycetemcomitans-induced autophagy in inflammatory response.

BACKGROUND
Aggressive periodontitis is characterized by the early-onset and rapid progression of periodontal destruction, and is closely associated with Aggregatibacter actinomycetemcomitans. Autophagy is a conserved process that is critical for removing damaged proteins, organelles, and even intracellular pathogens. Therefore, this study examined whether A. actinomycetemcomitans induces autophagy. In addition, the relationship among autophagy, bacterial internalization, and inflammatory molecules in periodontal aggressive inflammation was analyzed.


METHODS
The expression of autophagy-related proteins in human gingival tissue and THP-1 cells was assessed by Western blot analysis. The formation of light chain 3 (LC3) puncta was examined by confocal microscopy. The degree of bacterial internalization into the cells was determined by the viable cell count. Phagocytosis and ROS production were measured using confocal microscopy and flowcytometry.


RESULTS
When macrophages were infected with live A. actinomycetemcomitans, the autophagy influx was activated by the increase in LC3-II, autophagy-related gene (ATG)5/12, and Beclin-1 expression through the Toll-like receptors (TLR) and extracellular signal-regulated kinase (ERK) signaling pathways. The inhibition of A. actinomycetemcomitans-induced autophagy suppressed bacterial internalization via phagocytosis into the macrophages and increased interleukin-1β (IL-1β) production. Moreover, treatment with a ROS inhibitor inhibited these enhanced inflammatory responses.


CONCLUSIONS
A. actinomycetemcomitans-induced autophagy promotes bacterial internalization by phagocytosis, which restricts the excessive inflammatory response by down-regulating IL-1β and ROS production in macrophages. Thus, A. actinomycetemcomitans-induced autophagy and its role in regulating the inflammatory response may play an important role in the aggressive periodontal inflammatory process, and be a target for the development of new periodontal therapies. This article is protected by copyright. All rights reserved.