title: Actinobacillus actinomycetemcomitans-induced periodontal disease in mice: patterns of cytokine, chemokine, and chemokine receptor expression and leukocyte migration.
abstract: Although the pathogenesis of periodontal disease (PD) is not well known, cytokines, chemotactic factors and inflammatory cells are certainly involved in the disease outcome. Here, we characterized the evolution of the PD induced by Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of these bacteria leads to the migration of leukocytes to periodontal tissues and marked alveolar bone resorption. We found the expression of pro-inflammatory and Th1-type cytokines including TNF-alpha, IFN-gamma and IL-12 in periodontal tissues after infection with A. actinomycetemcomitans, from the early stages after infection and throughout the course of the disease. Similar kinetics of expression were found for the chemokines CCL5, CCL4, CCL3 and CXCL10 and for the receptors CCR5 and CXCR3, all of them linked to the Th1-type pattern. The expression of the Th2-type mediators IL-10, CCL1 and their receptors CCR4 and CCR8 was detected only after 30 days of infection, determining a time-dependent mixed pattern of polarized immune response. The chemokine expression was correlated with the presence of polymorphonuclear leukocytes, macrophages, CD4 and CD8 lymphocytes, and B cells in the inflammatory infiltrate. Interestingly, during the predominance of the Th1-type response, a sharp increase in the number of inflammatory cells and intense bone loss was seen. By contrast, after the increased expression of Th2-type mediators, the number of inflammatory cells remained constant. Our data demonstrate that mice subjected to oral inoculation of A. actinomycetemcomitans represent a useful model for the study of PD. In addition, our results suggest that expression of cytokines and chemokines can drive the selective recruitment of leukocyte subsets to periodontal tissues, which could determine the stable or progressive nature of the lesion.
authors.affiliation: School of Medicine-USP, Department of Biochemistry and Immunology, Avenue Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Avila-Campos
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Milanezi
authors.forename: Beatriz R
authors.initials: BR
authors.lastname: Ferreira
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D016301:Alveolar Bone Loss; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010510:Periodontal Diseases / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine