Antimicrobial and immunoregulatory effects mediated by human lung cells: role of IFN-gamma-induced tryptophan degradation.
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.
Heseler
Kathrin
K
Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-Universität Düsseldorf, Germany. kathrin.heseler@uni-duesseldorf.de
Spekker
Katrin
K
Schmidt
Silvia K
SK
MacKenzie
Colin R
CR
Däubener
Walter
W
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D008168:Lung / Q000276:immunology*; D018139:Simplexvirus / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014364:Tryptophan; C525396:1-methyltryptophan