The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Interferon-γ and Tumor Necrosis Factor-α Mediate the Upregulation of Indoleamine 2,3-Dioxygenase and the Induction of Depressive-Like Behavior in Mice in Response to Bacillus Calmette-Guérin
Open accessAbstract
Although the tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO), is a pivotal mediator of inflammation-induced depression, its mechanism of regulation has not yet been investigated in this context. Here, we demonstrate an essential role for interferon (IFN)γ and tumor necrosis factor (TNF)α in the induction of IDO and depressive-like behaviors in response to chronic immune activation. Wild-type (WT) control mice and IFNγR−−mice were inoculated with an attenuated form of Mycobacterium bovis, bacille Calmette-Guérin (BCG). Infection with BCG induced an acute episode of sickness that was similar in WT and IFNγR−−mice. Increased immobility during the forced swim and tail suspension tests occurred in WT mice 7 d after BCG inoculation but was entirely absent in IFNγR−−mice. In WT mice, these indices of depressive-like behavior were associated with chronic upregulation of IFNγ, interleukin(IL)-1β, TNFα, and IDO. Proinflammatory cytokine expression was elevated in BCG-infected IFNγR−−mice as well, but upregulation of lung and brain IDO mRNA was completely abolished. This was accompanied by an attenuation of BCG-induced TNFα mRNA and the lack of an increase in plasma kynurenine/tryptophan ratio in the BCG-inoculated IFNγR−−mice compared with WT controls. Pretreatment of mice with the TNFα antagonist, etanercept, partially blunted BCG-induced IDO activation and depressive-like behavior. In accordance with these in vivo data, IFNγ and TNFα synergized to induce IDO in primary microglia. Together, these data demonstrate that IFNγ, with TNFα, is necessary for induction of IDO and depressive-like behavior in mice after BCG infection.
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Citations
Cites
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Self-citationCytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
O'Connor, J. C., Lawson, M. A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002148 · Cited by 1,278
Self-citationTyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(05)67763-x · Cited by 1,069 · cited 1×
“While the role of specific cytokines in mediating chronic inflammation-induced (comorbid) depression is not yet understood, administration of the TNF inhibitor, etanercept, to patients with chronic psoriasis has been reported to alleviate symptoms of depression (Tyring et al., 2006).”
Henry, C. J., Huang, Y., Wynne, A., Hanke, M., Himler, J., Bailey, M. T., Sheridan, J. F., & Godbout, J. P. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-15 · Cited by 678
Monitoring tryptophan metabolism in chronic immune activation
Schröcksnadel, K., Wirleitner, B., Winkler, C., & Fuchs, D. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.06.013 · Cited by 551 · cited 2×
“That the plasma kynurenine/ tryptophan ratio did not follow this same pattern is likely because hepatic tryptophan dioxygenase (TDO) is the predominant tryptophan degrading enzyme at the periphery in the absence of inflammation (Schröcksnadel et al., 2006).”
Guillemin, G. J., Smythe, G., Takikawa, O., & Brew, B. J. (2005) · Glia · doi:10.1002/glia.20090 · Cited by 497 · cited 2×
“Activation of this ubiquitous enzyme by proinflammatory cytokines leads to the generation of several neuroactive metabolites including quinolic acid (QA), an NMDA receptor agonist that has been implicated in neurodegenerative disorders (Guillemin et al., 2005b; Spalletta et al., 2006).”
Interferon-alpha–induced changes in tryptophan metabolism
Capuron, L., Neurauter, G., Musselman, D. L., Lawson, D. H., Nemeroff, C. B., Fuchs, D., & Miller, A. H. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00173-2 · Cited by 493
O’Connor, J. C., McCusker, R. H., Strle, K., Johnson, R. W., Dantzer, R., & Kelley, K. W. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2007.09.010 · Cited by 238
Self-citation
Cited by
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
Leclercq, S., Matamoros, S., Cani, P. D., Neyrinck, A. M., Jamar, F., Stärkel, P., Windey, K., Tremaroli, V., Bäckhed, F., Verbeke, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415174111 · Cited by 972
Depression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944
The vascular depression hypothesis: mechanisms linking vascular disease with depression
Taylor, W. D., Aizenstein, H. J., & Alexopoulos, G. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.20 · Cited by 923
Metadata
- Authors
- O'Connor, J. C., André, C., Wang, Y., Lawson, M. A., Szegedi, S. S., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-04-01
- Volume
- 29
- Issue
- 13
- Pages
- 4200-4209
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2086208662
- Cited by
- 502
- References
- 9
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- O'Connor, J. C., André, C., Wang, Y., Lawson, M. A., Szegedi, S. S., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009). Interferon-γ and Tumor Necrosis Factor-α Mediate the Upregulation of Indoleamine 2,3-Dioxygenase and the Induction of Depressive-Like Behavior in Mice in Response to Bacillus Calmette-Guérin. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.5032-08.2009
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