Protective role for C3aR in experimental chronic pyelonephritis

作者全名："Zhao, Shu-Juan; Wu, Kun-Yi; Min, Xiao-Yun; Wang, Chun-Xuan; Cao, Bo; Ma, Ning; Yang, Xue-Ling; Zhu, Zhuo-Ran; Fu, Rong-Guo; Zhou, Wuding; Yang, Ju-Rong; Li, Ke"

作者地址："[Zhao, Shu-Juan; Wu, Kun-Yi; Min, Xiao-Yun; Cao, Bo; Ma, Ning; Zhu, Zhuo-Ran; Li, Ke] Xi An Jiao Tong Univ, Core Res Lab, Affiliated Hosp 2, Xian, Peoples R China; [Wang, Chun-Xuan; Yang, Xue-Ling; Yang, Ju-Rong] Chongqing Med Univ, Affiliated Hosp 3, Dept Nephrol, Chongqing 401120, Peoples R China; [Fu, Rong-Guo] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Nephrol, Xian, Peoples R China; [Zhou, Wuding] Kings Coll London, Fac Life Sci & Med, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London, England"

通信作者："Yang, JR (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Nephrol, Chongqing 401120, Peoples R China.; Li, K (通讯作者)，Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 2, Core Res Lab, Xian 710004, Peoples R China."

来源：FASEB JOURNAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000868772200001

JCR分区：Q1

影响因子：4.8

年份：2022

卷号：36

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：C3aR; chronic inflammation; chronic pyelonephritis; persistent infection; phagocytosis; renal fibrosis

摘要："Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar(-/-)) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar(-/-)) mice exhibited a similar disease phenotype to global C3ar(-/-) mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar(-/-) mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection."

基金机构："National Natural Science Foundation of China [81970596, 81900620]; Chongqing Talent Program Project [cstc2021ycjh-bgzxm0090]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Number: 81970596 and 81900620; The Chongqing Talent Program Project, Grant/Award Number: cstc2021ycjh-bgzxm0090"