Robert Dantzer

Director, Integrative Immunology and Behavior Program

Professor of Psychoneuroimmunology, Department of Pathology, College of Medicine; Department of Animal Sciences, College of ACES; Division of Nutritional Sciences and Neuroscience Program
Editor-in-Chief, Psychoneuroendocrinology
D.V.M., 1967, Toulouse, France
Ph.D., 1977, Toulouse, France

Research Areas

Interactions between the immune system and the brain

Together with Dr. Keith W. Kelley, our research group focuses on the behavioral and psychopathological consequences of the effects of inflammatory mediators on the brain. During the course of an inflammation the proinflammatory cytokines that are produced by peripheral innate immune cells alter brain functions via neural and humoral communication pathways. The brain forms an image of the peripheral immune response using the same cells and molecules as those mobilized at the periphery to fight infection. Brain cytokines induce sickness behavior, a well coordinated response of the host to help fighting infection, and this response is normally reversible. When the brain cytokine system is no longer regulated such as during chronic inflammation or in the presence of vulnerability factors, this response eventually culminates in psychiatric disorders such as depression. At the experimental level we explore the mechanisms that are responsible for the transition from sickness to depression, with an emphasis on the tryptophan degrading enzyme indoleamine 2,3 dioxygenase that is induced by immune mediators. Degradation of tryptophan by this enzyme can generate neurotoxic metabolites. At the clinical level, we collaborate with other investigators to study the possibility that the subjective health complaints (e.g., fatigue, depressed mood) of patients suffering from chronic inflammatory disorders are mediated by inflammation and can be attenuated by interventions that attenuate inflammation (e.g., physical exercise).

Representative Publications

Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, Spivey JR, Saito K and Miller AH (2010) CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression, Mol Psychiatry 15(4):393-403.

O'Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW and Dantzer R (2009) Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin, J Neurosci. 29(13):4200-9.

O'Connor JC, Lawson MA, André C, Briley EM, Szegedi SS, Lestage J, Castanon N, Herkenham M, Dantzer R and Kelley KW (2009)Induction of IDO by bacille Calmette-Guérin is responsible for development of murine depressive-like behavior, J Immunol 182(5):3202-12.

O'Connor JC, Lawson MA, André C, Moreau M, Lestage J, Castanon N, Kelley KW and Dantzer R (2009) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice, Mol Psychiatry, 14(5):511-22.

Dantzer R, O'Connor JC, Freund GG, Johnson RW, and Kelley KW. (2008) From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neurosci, 9(1): 46-56.

Dantzer R, Capuron L, Irwin MR, Miller AH, Ollat H, Hugh Perry V, Rousey S, and Yirmiya R. (2008) Identification and treatment of symptoms associated with inflammation in medically ill patients. Psychoneuroendocrinology, 33(1): 18-29.

Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O' Connor J, Castanon N, Kelley KW, Dantzer R and Johnson RW (2008) Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system, Neuropsychopharmacology 33(10):2341-51.

Moreau M, André C, O'Connor JC, Dumich SA, Woods JA, Kelley KW, Dantzer R, Lestage J and Castanon N (2008) Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior, Brain Behav Immun, 22(7):1087-95.

Dantzer R, and Kelley KW. (2007) Twenty years of research on cytokine-induced sickness behavior, Brain Behav Immun, 21, 153-160.

Johnson DR, O'Connor JC, Dantzer R and Freund GG (2005) Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness, Proc Natl Acad Sci U S A, 102(42):15184-9.

Additional Information

Collaborative projects

Dr. A. Kavelaars – A novel neuroimmune risk factor for comorbid depression and chronic pain

Professor K.W.Kelley – Aids, immune activation and mental health

Professor K.W. Kelley – Neuroimmune mechanisms of depressive–like behavior during aging

Professor R.W. Johnson – Neuroinflammation and behavior in the aged

Professor S. Donovan – Training in inflammation and nutritional dysfunction

Dr. R.H. McCusker – Neuroimmunology and behavior: Natural antagonism of sickness and depression

Dr. J.C. O'Connor – Biobehavioral role of brain kynurenine metabolism in mental illness

Lab

Robert Dantzer shares office and laboratory space with Professor Keith W. Kelley in 227, 250 and 261 ERML, respectively.