{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:16:16Z","timestamp":1761920176358,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO) provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO-mediated broad-spectrum effector functions have never been observed under hypoxia<jats:italic>in vitro<\/jats:italic>, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO and<jats:italic>ex vivo<\/jats:italic>murine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites) and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occur<jats:italic>in vivo<\/jats:italic>. This might be detrimental for the appropriate host immune response towards relevant pathogens.<\/jats:p>","DOI":"10.1155\/2016\/1638916","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T00:17:49Z","timestamp":1470183469000},"page":"1-11","source":"Crossref","is-referenced-by-count":6,"title":["Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function"],"prefix":"10.1155","volume":"2016","author":[{"given":"Frank","family":"Elbers","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Woite","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, 40225 D\u00fcsseldorf, 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