The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice.
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.
Garlet
Gustavo P
GP
Department of Biological Sciences, Bauru School of Dentistry, Al. Octávio Pinheiro Brisola, 9-75, CEP 17012-901, Bauru, Sao Paulo, Brazil. garletgp@usp.br
Cardoso
Cristina R B
CR
Campanelli
Ana P
AP
Garlet
Thiago P
TP
Avila-Campos
Mario J
MJ
Cunha
Fernando Q
FQ
Silva
João S
JS
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
D004269:DNA, Bacterial; D018836:Inflammation Mediators; D007371:Interferon-gamma; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse