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The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> have differential virulence factor expression, <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> cytolethal distending toxin (<jats:styled-content style=\"fixed-case\">CDT<\/jats:styled-content>), leukotoxin, and lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> employs <jats:styled-content style=\"fixed-case\">CDT<\/jats:styled-content>, leukotoxin, and <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This <jats:italic>supra<\/jats:italic>\u2010physiologic 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\u2010hematopoietic and hematopoietic. Non\u2010hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid\u2010derived 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 <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> will be discussed to further delineate immune cell mechanisms during <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> infection. Finally, we will discuss the osteo\u2010immunomodulatory effects induced by <jats:italic>A.\u00a0actinomycetemcomitans<\/jats:italic> and dissect the catabolic disruption of balanced osteoclast\u2013osteoblast\u2010mediated bone remodeling, which subsequently leads to net\u00a0alveolar bone loss.<\/jats:p>","DOI":"10.1111\/omi.12119","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T09:55:45Z","timestamp":1437558945000},"page":"207-227","source":"Crossref","is-referenced-by-count":120,"title":["<i>Aggregatibacter actinomycetemcomitans<\/i>, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis"],"prefix":"10.1111","volume":"31","author":[{"given":"B.A.","family":"Herbert","sequence":"first","affiliation":[{"name":"Department of Oral Health Sciences and the Center for Oral Health Research Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.M.","family":"Novince","sequence":"additional","affiliation":[{"name":"Department of Oral Health Sciences and the Center for Oral Health Research Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.L.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Department of Oral Health Sciences and the Center for Oral Health Research Medical University of South Carolina Charleston SC USA"},{"name":"Department of Microbiology and Immunology Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1099\/0022-1317-50-10-860","article-title":"Prevalence of cdtABC genes encoding cytolethal distending toxin among Haemophilus ducreyi and Actinobacillus actinomycetemcomitans strains","volume":"50","author":"Ahmed H.J.","year":"2001","journal-title":"J Med Microbiol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/0377-4929.44994"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2376"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2012.01.014"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1999.4.1.1"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.1.403"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1989.tb00106.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00063"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2012.01871.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.6.2780-2786.2002"},{"key":"e_1_2_6_12_1","first-page":"151","article-title":"Remaniement de l'os alveolaire et des fibres desmodontales au cours de la migration physiologique","volume":"1","author":"Baron R.","year":"1973","journal-title":"J Biol Buccale"},{"key":"e_1_2_6_13_1","unstructured":"Baron R.(1977)Importance of the intermediate phases between resorption and formation in the measurement and understanding of the bone remodeling sequence. 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