Tuesday, January 22, 2008

Role of IFN-gamma-induced tryptophan degradation

FEMS Immunol Med Microbiol. 2008 Jan 16 [Epub ahead of print]

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

Heseler K, Spekker K, Schmidt SK, Mackenzie CR, Däubener W

Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-Universität Düsseldorf, Germany.

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-gamma-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-alpha (TNF-alpha). Furthermore, the IFN-gamma-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-gamma-induced antimicrobial effects mediated by lung cells. Therefore it is suggested that tryptophan depletion via IFN-gamma-mediated IDO induction is a major antibacterial, antiparasitic, antiviral and immunoregulatory mechanism in human lung cells.

PMID: 18205804 [PubMed - as supplied by publisher]

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