Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
Immunity. 2014 Apr 17;40(4):621-32. doi: 10.1016/j.immuni.2014.02.015.
Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.
尿路的免疫具有独特且尚未充分理解的病理生理学特征，尿路感染 (UTI) 是发病率和死亡率的重要原因。我们研究了可溶性模式识别分子五聚素 3 (PTX3) 在 UTI 中的作用，PTX3 是先天免疫体液臂的关键组成部分。PTX3 缺陷型小鼠对 UTI 的控制能力受损，炎症加剧。尿路致病性大肠杆菌 (UPEC) 通过 Toll 样受体 4 (TLR4) 和 MyD88 依赖性方式诱导尿路上皮细胞表达 PTX3。PTX3 增强中性粒细胞对 UPEC 的吞噬作用和吞噬体成熟。PTX3 可在 UTI 患者的尿液中检测到，其含量与疾病严重程度相关。在易患 UTI 的患者队列中，PTX3 基因多态性与急性肾盂肾炎和膀胱炎的易感性相关。这些结果表明，PTX3 是先天抵抗 UTI 的必需组成部分。因此，先天免疫的细胞和体液臂在介导对 UTI 的抵抗方面发挥互补作用。
