The essential role of IFN-γ in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice

• Published in: Microbes and infection 2008-04, Vol.10 (5), p.489-496
• Main Authors: Garlet, Gustavo P., Cardoso, Cristina R.B., Campanelli, Ana P., Garlet, Thiago P., Avila-Campos, Mario J., Cunha, Fernando Q., Silva, João S.
• Format: Article
• Language: English
• Subjects: Actinobacillus Infections - immunology; Actinobacillus Infections - metabolism; Acute-Phase Reaction - immunology; Aggregatibacter actinomycetemcomitans; Aggregatibacter actinomycetemcomitans - immunology; Alveolar Bone Loss - immunology; Alveolar Bone Loss - metabolism; Alveolar Bone Loss - microbiology; Animals; Biological and medical sciences; DNA, Bacterial - isolation & purification; Fundamental and applied biological sciences. Psychology; IFN-γ; Immunocompromised Host; Inflammation Mediators - analysis; Interferon-gamma - deficiency; Interferon-gamma - immunology; Male; Maxillary Diseases - immunology; Maxillary Diseases - metabolism; Maxillary Diseases - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Nitric Oxide Synthase Type II - analysis; Periodontal diseases; Periodontitis - immunology; Periodontitis - metabolism; Periodontitis - microbiology; Peroxidase - analysis
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2008.01.010

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-γ modulates the outcome of Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice. Our results showed that IFN-γ 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-γ 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-γ 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-γ mediated cell migration to diseased periodontal tissues, and its essential role to control A. actinomycetemcomitans infection were clarified.