ABSTRACT
The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of Gata3- and Foxp3-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress.
Subject(s)
Adrenal Cortex Hormones/metabolism , Brain/immunology , Stress, Psychological/metabolism , Adrenal Cortex Hormones/cerebrospinal fluid , Adrenal Cortex Hormones/immunology , Animals , Behavior, Animal , Brain/metabolism , Choroid Plexus/metabolism , Choroid Plexus/physiopathology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , GATA3 Transcription Factor/metabolism , Hormone Antagonists/pharmacology , Humans , Mice, Inbred C57BL , Mice, Mutant Strains , Mifepristone/pharmacology , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Signal Transduction , Single-Cell Analysis , Stress, Psychological/immunology , T-Lymphocytes/immunologyABSTRACT
Thirty-three patients have been investigated in Townsville between 1983 and 1987 with eosinophilic enteritis. All were Caucasian and had been well prior to this illness. Twenty-six had similar presentations with episodic and transient abdominal pain often with features of small bowel obstruction. Four patients presented with pain and diarrhoea, two with chronic diarrhoea and one with recurrent melena. All patients at some stage during their illness developed high peripheral blood eosinophil counts, mean value 2096/mm3. Nine patients had laparotomies. The disease typically involved a short segment of ileum or jejunum with thickening and induration. The histology of the four resected specimens demonstrated a transmural inflammation with edema and an intense eosinophilic infiltrate. A solitary adult hookworm was identified in one patient adherent to the mucosa of the resected bowel. Each of the 19 patients treated with antihelminthic drugs responded promptly. Recovery was accompanied by a return to normal peripheral blood eosinophil counts. This paper reports an unusual form of eosinophilic enteritis thought due to a parasitic infection. The diagnosis should be considered in patients from North Queensland presenting with abdominal pain and eosinophilia. Laparotomy should be delayed pending a trial of conservative therapy with mebendazole.
