Antimicrobial and immunoregulatory effects mediated by human lung cells: role of IFN-γ-induced tryptophan degradation |
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Authors: | Kathrin Heseler,Katrin Spekker,Silvia K. Schmidt,Colin R. MacKenzie,& Walter Dä ubener |
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Affiliation: | Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-Universität Düsseldorf, Germany |
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Abstract: | 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. |
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Keywords: | indoleamine 2,3-dioxygenase lung cells Toxoplasma Staphylococcus herpes simplex virus immunoregulation |
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