Eur J Immunol. 2009 Jul 27. [Epub ahead of print]
Antimicrobial and immunoregulatory properties of human tryptophan 2,3-dioxygenase
Schmidt SK, Müller A, Heseler K, Woite C, Spekker K, Mackenzie CR, Däubener W.
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Germany.
In mammals the regulation of local tryptophan concentrations by the interferon-gamma inducible enzyme indoleamine 2,3-dioxygenase (IDO) is a prominent antimicrobial and immunoregulatory effector mechanism. Here, we show for the first time that another tryptophan degrading enzyme, the liver specific tryptophan 2,3-dioxygenase (TDO), is also capable of mediating antimicrobial and immunoregulatory effects.Using a tetracycline inducible eukaryotic system, we were able to express recombinant TDO protein, which exhibits functional properties of native TDO. We found that HeLa cells expressing recombinant TDO were capable of inhibiting the growth of bacteria (Staphylococcus aureus), parasites (Toxoplasma gondii) and viruses (herpes simplex virus). These TDO-mediated antimicrobial effects could be blocked by the addition of tryptophan.In addition we observed that, similar to IDO-positive cells, TDO-positive cells, were capable of inhibiting anti CD3-driven T cell proliferation and IFN- production. Furthermore, TDO-positive cells also restricted alloantigen induced T cell activation.Here, we describe for the first time that TDO mediates antimicrobial and immunoregulatory effects and suggest that TDO-dependent inhibition of T cell growth might be involved in the immunotolerance observed in vivo during allogeneic liver transplantation.
PMID: 19637229 [PubMed - as supplied by publisher]