Journal
JOURNAL OF IMMUNOLOGY
Volume 187, Issue 2, Pages 635-643Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1003034
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Funding
- National Institutes of Health/National Institute of Allergy and Infectious Diseases Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research Program
- Region V Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research Program (National Institutes of Health) [1-U54-AI-057153]
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [1-T32-AI-065411]
- National Research Service
- American Cancer Society Ohio Division
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The environmental bacterium Burkholderia cenocepacia causes opportunistic lung infections in immunocompromised individuals, particularly in patients with cystic fibrosis. Infections in these patients are associated with exacerbated inflammation leading to rapid decay of lung function, and in some cases resulting in cepacia syndrome, which is characterized by a fatal acute necrotizing pneumonia and sepsis. B. cenocepacia can survive intracellularly in macrophages by altering the maturation of the phagosome, but very little is known on macrophage responses to the intracellular infection. In this study, we have examined the role of the PI3K/Akt signaling pathway in B. cenocepacia-infected monocytes and macrophages. We show that PI3K/Akt activity was required for NF-kappa B activity and the secretion of proinflammatory cytokines during infection with B. cenocepacia. In contrast to previous observations in epithelial cells infected with other Gram-negative bacteria, Akt did not enhance I kappa B kinase or NF-kappa B p65 phosphorylation, but rather inhibited GSK3 beta, a negative regulator of NF-kappa B transcriptional activity. This novel mechanism of modulation of NF-kappa B activity may provide a unique therapeutic target for controlling excessive inflammation upon B. cenocepacia infection. The Journal of Immunology, 2011, 187: 635-643.
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