A Crucial Role for Tryptophan Catabolism at the Host/Candida albicansInterface
Open Access
- 1 March 2005
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 174 (5), 2910-2918
- https://doi.org/10.4049/jimmunol.174.5.2910
Abstract
By mediating tryptophan catabolism, the enzyme indoleamine 2,3-dioxygenase (IDO) has a complex role in immunoregulation in infection, pregnancy, autoimmunity, transplantation, and neoplasia. We hypothesized that IDO might affect the outcome of the infection in mice infected with Candida albicans by virtue of its potent regulatory effects on inflammatory and T cell responses. IDO expression was examined in mice challenged with the fungus along with the consequences of its blockade by in vivo treatment with an enzyme inhibitor. We found that IDO activity was induced at sites of infection as well as in dendritic cells and effector neutrophils via IFN-γ- and CTLA-4-dependent mechanisms. IDO inhibition greatly exacerbated infection and associated inflammatory pathology as a result of deregulated innate and adaptive/regulatory immune responses. However, a role for tryptophan catabolism was also demonstrated in a fungus-autonomous fashion; its blockade in vitro promoted yeast-to-hyphal transition. These results provide novel mechanistic insights into complex events that, occurring at the fungus/pathogen interface, relate to the dynamics of host adaptation to the fungus. The production of IFN-γ may be squarely placed at this interface, where IDO activation probably exerts a fine control over fungal morphology as well as inflammatory and adaptive antifungal responses.Keywords
This publication has 48 references indexed in Scilit:
- CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86Nature Immunology, 2004
- Immunity to fungal infectionsNature Reviews Immunology, 2004
- In this issueNature Reviews Immunology, 2004
- Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-DioxygenaseScience, 2002
- The role of IFN-γ in the outcome of chlamydial infectionCurrent Opinion in Immunology, 2002
- Enhancement of Innate Immunity againstMycobacterium aviumInfection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-DioxygenaseInfection and Immunity, 2001
- Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?Immunology Today, 1999
- Immunity to Candida albicans: Th1, Th2 cells and beyondCurrent Opinion in Microbiology, 1999
- Interferon‐γ‐Induced Activation of Indoleamine 2,3‐Dioxygenase in Cord Blood Monocyte‐Derived Macrophages Inhibits the Growth of Group B StreptococciThe Journal of Infectious Diseases, 1998
- Interleukin‐12 but not interferon‐γ production correlates with induction of T helper type‐1 phenotype in murine candidiasisEuropean Journal of Immunology, 1994