title: The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice.
abstract: Inflammatory immune reactions in response to periodontopathogens trigger periodontal destruction, but their role to protect the host against infection remains unknown. Thus, we examined the mechanisms by which IFN-gamma modulates the outcome of Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice. Our results showed that IFN-gamma deficient mice developed less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significant lower alveolar bone loss and inflammatory reaction. However, the absence of IFN-gamma results in increased bacterial load in periodontal tissues and higher acute phase reaction, followed by a disseminated bacterial infection and mice death during the course of the disease. Such impaired host response was found to be associated with a reduction in the levels of inflammatory cytokines and chemokines and in the number of GR1+, F4/80+, CD4+ and CD8+ leukocytes in the diseased periodontium of IFN-gamma deficient mice. In addition, the levels of both antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase were also found to be reduced in IFN-KO mice. Our results demonstrate for the first time that a periodontal infection may be lethal in an immunocompromised host. In addition, the mechanisms involved in IFN-gamma mediated cell migration to diseased periodontal tissues, and its essential role to control A. actinomycetemcomitans infection were clarified.
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, Al. Octávio Pinheiro Brisola, 9-75, CEP 17012-901, Bauru, Sao Paulo, Brazil. garletgp@usp.br
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.forename: Cristina R B
authors.initials: CR
authors.lastname: Cardoso
authors.forename: Ana P
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Thiago P
authors.initials: TP
authors.lastname: Garlet
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Avila-Campos
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology* / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000276:immunology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D004269:DNA, Bacterial / Q000302:isolation & purification; D016867:Immunocompromised Host; D018836:Inflammation Mediators / Q000032:analysis; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008297:Male; D008439:Maxillary Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009195:Peroxidase / Q000032:analysis
chemical_list: D004269:DNA, Bacterial; D018836:Inflammation Mediators; D007371:Interferon-gamma; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse