Liu Yaxiao, Wang Jinhua, Lin Junyang, Sun Dingqi, Zhu Kejia, Diao Tongxiang, Fu Qiang, Ren Qingyu
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Radiotherapy, Shandong Second Provincial General Hospital, Jinan, China.
JCI Insight. 2025 Mar 18;10(9). doi: 10.1172/jci.insight.189362. eCollection 2025 May 8.
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.
尿路感染（UTIs）是临床实践中最常见的感染之一，其中心理压力是调节免疫功能的关键病理因素。然而，大脑中的应激网络与膀胱感染之间的机制途径仍知之甚少。在本研究中，我们发现急性应激处理可抑制UTIs小鼠的膀胱炎症，并且在这些小鼠的室旁核（PVN）脑区观察到大量神经元显示炎症相关标志物与逆行标记之间存在重叠。激活PVN可减轻尿路致病性大肠杆菌诱导的膀胱炎症反应。此外，阻断下丘脑-垂体-肾上腺轴可逆转急性应激介导的抗炎反射，表明糖皮质激素可能通过脑-体回路调节UTIs。膀胱免疫细胞的单细胞RNA测序显示，2型固有淋巴细胞（ILC2）表达大量糖皮质激素受体。PVN的激活通过直接调节细胞内糖皮质激素信号传导，有效抑制ILC2细胞促炎细胞因子集落刺激因子2的表达。最终，我们的研究对UTI治疗的脑-体回路定位具有启示意义。
