Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis

Abstract

Summary Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and pre-clinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast mediated bone remodeling, which subsequently leads to net alveolar bone loss.

Long‐term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study

“…Despite earlier studies reporting positive clinical results following treatment of this disease with mechanical debridement alone (Saxen et al, 1986), this regimen has resulted in certain limitations, especially regarding the control of invading and highly pathogenic microorganisms on oral tissues, such as the Aggregatibacter actinomycetemcomitans ( Aa ) (Meyer et al, 1996, Christersson et al, 1985, Xajigeorgiou et al, Christersson and Zambon, 1993, Herbert et al, 2015, Aberg et al, 2015). Thus, the combination of mechanical treatment with adjunctive Abx has been suggested in the treatment of aggressive periodontitis in an attempt to successfully reduce pathogenic bacteria, especially Aa , which has been long and strongly associated with this disease (Darby and Curtis, 2001), including in the population studied here (Shaddox et al, 2012).…”

Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss

“…These monocytes are lymphoid negative and myeloid positive, and they are defined as B220 Ϫ CD3 Ϫ NK1.1 Ϫ CD11b ϩ Ly6C hi CD115 ϩ CCR2 hi CX3CR1 ϩ common lineage cells (22). Hematopoietic system-derived host immune cells include macrophages, neutrophils, dendritic cells, T cells, and osteoclasts, all of which have been shown to respond to A. actinomycetemcomitans in vitro (23). Nonhematopoietic cell types, including epithelial cells, fibroblasts, and osteoblasts, are also involved in A. actinomycetemcomitans pathogenesis.…”

Virulence factors associated withAggregatibacter actinomycetemcomitansand their role in promoting periodontal diseases

“…7 The periodontopathogen Aggregatibacter actinomycetemcomitans is a gram-negative bacterium that colonizes the gingival sulcus and invades the epithelial tissues by proapoptotic virulence mechanisms and stimulates the expression of proinflammatory cytokines. 8 A. actinomycetemcomitans is present in individuals' health conditions in the microbiota, but it can also become the largest colony in cases of aggressive periodontitis, which destroys dental support tissues. 9 The qualitative and quantitative relation of subgingival biofilm as well as lifestyle and genetic predisposition are factors that help the disease become established.…”

“…22,24 The treatment of periodontal disease is based on virulence factors, the microorganisms that are established in the processes of health and disease; therefore, the treatments must aim to control these microorganisms. 4,8,9 It is necessary to understand the role of bacterial biofilm in the etiology of periodontal diseases, as the severity and progression of these diseases are determined in large part by factors related to the host's response. 25,26 The results regarding BiIRI are noteworthy because they show what an IDP is and that gene deletion causes a reduction in the internalization of the cytokine IL-1B by the microorganism A. actinomycetemcomitans; an IDP acts as a nonspecific agent that causes the surface concentration.…”