Antimicrobial and immunoregulatory effects mediated by human lung cells: role of IFN-γ-induced tryptophan degradation

• Published in: FEMS immunology and medical microbiology 2008-03, Vol.52 (2), p.273-281
• Main Authors: Heseler, Kathrin, Spekker, Katrin, Schmidt, Silvia K, MacKenzie, Colin R, Däubener, Walter
• Format: Article
• Language: English
• Subjects: Abscesses; Alveoli; Animals; Antiinfectives and antibacterials; Antiparasitic agents; Bacteriology; Biodegradation; Biological and medical sciences; Bronchus; Cell activation; Cell Line; Cell proliferation; Depletion; Enzyme Inhibitors - pharmacology; Epithelial cells; Fundamental and applied biological sciences. Psychology; Herpes simplex; herpes simplex virus; Herpes viruses; Humans; Immunocompromised hosts; Immunoregulation; indoleamine 2,3-dioxygenase; Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Interferon; Interferon-gamma - immunology; Interleukin 1; Interleukin-1 - immunology; Lung - immunology; lung cells; Lungs; Lymphocytes; Lymphocytes T; Microbiology; Microorganisms; Miscellaneous; Parasitic diseases; Pathogens; Physicians; Pneumonia; Simplexvirus - immunology; Staphylococcus; Staphylococcus aureus - immunology; Supplements; Toxoplasma; Toxoplasma - immunology; Tryptophan; Tryptophan - analogs & derivatives; Tryptophan - metabolism; Tryptophan - pharmacology; Tryptophan 2,3-dioxygenase; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Virology; Viruses; γ-Interferon
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.2007.00374.x

Pneumonia caused by bacterial, viral and parasitic pathogens is one of the most common clinical problems facing primary and secondary care physicians. Staphylococcus aureus is a common cause of lung abscesses in humans and, in immunocompromised patients, herpes simplex virus type I and Toxoplasma gondii can cause severe life-threatening pneumonia. The authors focused their interest in the antimicrobial effects mediated by human lung cells against these pathogens. It was found that IFN-γ-stimulated lung cells are capable of inhibiting T cell proliferation and restrict the replication of microorganisms such as T. gondii, S. aureus and herpes simplex virus. This immunoregulatory and antimicrobial effect was enhanced in the presence of IL-1 or tumor necrosis factor-α (TNF-α). Furthermore, the IFN-γ-dependent antimicrobial effects of HBE4-E6/E7 (human lung bronchus epithelial cells) and A549 (human type II alveolar cells) correlated with the activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). It was found that both the abrogation of IDO activity by the specific IDO-inhibitor 1- l-methyltryptophan and the supplementation of cultures with tryptophan result in an inhibition of IFN-γ-induced antimicrobial effects mediated by lung cells. Therefore it is suggested that tryptophan depletion via IFN-γ-mediated IDO induction is a major antibacterial, antiparasitic, antiviral and immunoregulatory mechanism in human lung cells.