PDF(Pubmed)
Abstract：
UNASSIGNED: Urinary tract infections (UTIs) can evoke a rapid host immune response leading to bladder inflammation and epithelial damage. Neuroimmune interactions are critical for regulating immune function in mucosal tissues. Yet the role of nociceptor neurons in bladder host defense has not been well defined. This study aimed to explore the interaction between nociceptor neurons and bladder immune system during UTIs.
UNASSIGNED: In this study, whether uropathogenic Escherichia coli (UPEC) and lipopolysaccharide (LPS) can directly stimulate nociceptor neurons was detected. Female C57BL/6J mice were treated with high dose of capsaicin, a high-affinity TRPV1 agonist, to ablate nociceptor neurons. Bladder inflammation, barrier epithelial function and bladder immune cell infiltration were assessed after UPEC infection. The level of neuropeptide calcitonin gene-related peptide (CGRP) in infected bladder was detected. Furthermore, the effects of CGRP on neutrophils and macrophages were evaluated both in vitro and in vivo.
UNASSIGNED: We found that UPEC and its pathogenic factor LPS could directly excite nociceptor neurons, releasing CGRP into infected bladder, which suppressed the recruitment of neutrophils, the polarization of macrophages and the killing function of UPEC. Both Botulinum neurotoxin A (BoNT/A) and BIBN4096 (CGRP antagonism) blocked neuronal inhibition and prevented against UPEC infection.
UNASSIGNED: The present study showed a novel mechanism by which UPEC stimulated the secretion of CGRP from nociceptor neurons to suppress innate immunity.
UNASSIGNED: In this study, whether uropathogenic Escherichia coli (UPEC) and lipopolysaccharide (LPS) can directly stimulate nociceptor neurons was detected. Female C57BL/6J mice were treated with high dose of capsaicin, a high-affinity TRPV1 agonist, to ablate nociceptor neurons. Bladder inflammation, barrier epithelial function and bladder immune cell infiltration were assessed after UPEC infection. The level of neuropeptide calcitonin gene-related peptide (CGRP) in infected bladder was detected. Furthermore, the effects of CGRP on neutrophils and macrophages were evaluated both in vitro and in vivo.
UNASSIGNED: We found that UPEC and its pathogenic factor LPS could directly excite nociceptor neurons, releasing CGRP into infected bladder, which suppressed the recruitment of neutrophils, the polarization of macrophages and the killing function of UPEC. Both Botulinum neurotoxin A (BoNT/A) and BIBN4096 (CGRP antagonism) blocked neuronal inhibition and prevented against UPEC infection.
UNASSIGNED: The present study showed a novel mechanism by which UPEC stimulated the secretion of CGRP from nociceptor neurons to suppress innate immunity.
摘要：
■尿路感染（UTI）可以引起快速的宿主免疫反应，导致膀胱炎症和上皮损伤。神经免疫相互作用对于调节粘膜组织的免疫功能至关重要。然而，伤害性感受器神经元在膀胱宿主防御中的作用尚未得到很好的定义。本研究旨在探讨UTI过程中伤害性感受器神经元与膀胱免疫系统之间的相互作用。
■在这项研究中，检测尿路致病性大肠杆菌(UPEC)和脂多糖(LPS)是否能直接刺激伤害性感受器神经元。用高剂量的辣椒素治疗雌性C57BL/6J小鼠，一种高亲和力的TRPV1激动剂，消融痛觉感受器神经元。膀胱炎症,评估UPEC感染后的屏障上皮功能和膀胱免疫细胞浸润。检测感染膀胱中神经肽降钙素基因相关肽（CGRP）的水平。此外，在体外和体内评估CGRP对中性粒细胞和巨噬细胞的影响。
■我们发现UPEC及其致病因子LPS可以直接兴奋伤害感受器神经元，将CGRP释放到感染的膀胱中，抑制了中性粒细胞的募集，巨噬细胞的极化和UPEC的杀伤功能。肉毒杆菌神经毒素A(BoNT/A)和BIBN4096(CGRP拮抗作用)均阻断神经元抑制并防止UPEC感染。
■本研究显示了一种新的机制，UPEC通过该机制刺激伤害性感受器神经元分泌CGRP以抑制先天免疫。
■在这项研究中，检测尿路致病性大肠杆菌(UPEC)和脂多糖(LPS)是否能直接刺激伤害性感受器神经元。用高剂量的辣椒素治疗雌性C57BL/6J小鼠，一种高亲和力的TRPV1激动剂，消融痛觉感受器神经元。膀胱炎症,评估UPEC感染后的屏障上皮功能和膀胱免疫细胞浸润。检测感染膀胱中神经肽降钙素基因相关肽（CGRP）的水平。此外，在体外和体内评估CGRP对中性粒细胞和巨噬细胞的影响。
■我们发现UPEC及其致病因子LPS可以直接兴奋伤害感受器神经元，将CGRP释放到感染的膀胱中，抑制了中性粒细胞的募集，巨噬细胞的极化和UPEC的杀伤功能。肉毒杆菌神经毒素A(BoNT/A)和BIBN4096(CGRP拮抗作用)均阻断神经元抑制并防止UPEC感染。
■本研究显示了一种新的机制，UPEC通过该机制刺激伤害性感受器神经元分泌CGRP以抑制先天免疫。
