Abstract
Urinary tract infections (UTIs) are one of the most commonly encountered infections in clinical practice, in which psychological stress is a critical pathological contributor to modulate immune function. However, mechanistic pathways linking stress networks in the brain to bladder infection remain poorly understood. In this study, we discovered that acute stress treatment suppressed bladder inflammation in mice with UTIs, and a substantial number of neurons showing overlap between inflammation-associated markers and retrograde labeling were observed in the paraventricular nucleus (PVN) brain region of these mice. Activation of the PVN alleviated uropathogenic Escherichia coli–induced bladder inflammatory response. Moreover, a blocked hypothalamic-pituitary-adrenal axis reversed the antiinflammatory reflex mediated by acute stress, suggesting that glucocorticoids may modulate UTIs through the brain-body circuit. Single-cell RNA-Seq of bladder immune cells revealed that type 2 innate lymphoid (ILC2) cells expressed abundant levels of glucocorticoid receptor. The activation of the PVN effectively inhibited the expression of the pro-inflammatory cytokine colony-stimulating factor 2 by ILC2 cells through direct regulation of cell-intrinsic glucocorticoid signaling. Ultimately, our study has implications for the positioning of the brain-body circuit for UTI treatment.
Authors
Yaxiao Liu, Jinhua Wang, Junyang Lin, Dingqi Sun, Kejia Zhu, Tongxiang Diao, Qiang Fu, Qingyu Ren
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