Protective role for C3aR in experimental chronic pyelonephritis
Protective role for C3aR in experimental chronic pyelonephritis
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C3aR 在实验性慢性肾盂肾炎中的保护作用
DOI：
10.1096/fj.202201007r
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发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Ke Li
中科院分区：
文献类型：
--
作者：
Shu‐Juan Zhao;Kun‐Yi Wu;Xiao‐Yun Min;Chun‐Xuan Wang;Bo Cao;Ning Ma;Xue‐Ling Yang;Zhuo‐Ran Zhu;Rong‐Guo Fu;Wuding Zhou;Ju‐Rong Yang;Ke Li
新的证据表明C3 aR在体内平衡、宿主防御和疾病中起重要作用。尽管已知C3 aR在几种急性细菌感染模型中具有保护作用，但C3 aR在慢性感染中的作用在很大程度上是未知的。在这里，我们表明，C3 aR是保护实验性慢性肾盂肾炎。总体C3 aR缺陷（C3 ar −/−）小鼠肾脏感染尿路致病性大肠杆菌后，肾脏细菌负荷更高，肾脏组织学病变更明显，肾脏凋亡细胞积聚、组织炎症和细胞外基质沉积增加。大肠杆菌（UPEC）菌株IH 11128中的表达。髓样C3 aR缺陷（Lyz 2-C3 ar −/−）小鼠表现出与全局C3 ar −/−小鼠相似的疾病表型。用C3 aR激动剂的药物治疗降低了实验性慢性肾盂肾炎的疾病严重程度。此外，C3 ar −/−小鼠的巨噬细胞吞噬UPEC的能力受损。我们的数据清楚地表明C3 aR对实验性慢性肾盂肾炎的保护作用，巨噬细胞C3 aR在保护中起主要作用，并且C3 aR是巨噬细胞吞噬UPEC所必需的。我们观察到C3 aR激动剂减少了病理学，这表明C3 aR激活在慢性感染中具有治疗潜力。
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.
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DOI：
10.1038/nrneph.2016.70
发表时间：
2016-07
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
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通讯作者：
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影响因子：
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DOI：
10.1096/fj.202000384r
发表时间：
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期刊：
The FASEB Journal
影响因子：
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影响因子：
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通讯作者：
Förster, I