Sundac Lana, Dando Samantha J, Sullivan Matthew J, Derrington Petra, Gerrard John, Ulett Glen C
Department of Health, Pathology Queensland, Queensland Government, Gold Coast University Hospital, Gold Coast, Queensland 4211, Australia.
School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Gold Coast, Queensland 4222, Australia.
Pathog Dis. 2016 Aug;74(6). doi: 10.1093/femspd/ftw062. Epub 2016 Jun 27.
Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24-48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis.
由尿路致病性大肠杆菌(UPEC)引起的尿路感染(UTIs)是人类常见的感染。尽管这些感染造成了巨大的医疗成本,但患者症状出现后立即发生的与感染相关的人体免疫反应仍很大程度上未明确。我们进行了一项前瞻性研究,旨在确定因UPEC导致急性膀胱炎而入院的成年住院患者在入院后24 - 48小时内尿液细胞因子的情况。使用27靶点多重蛋白质分析对尿液样本进行分析,用于生成患者的免疫图谱,并与年龄和性别匹配的健康对照进行比较。感染导致尿液中多种促炎细胞因子水平显著升高,这一观察结果与先前在小鼠模型和临床文献中的发现一致。我们还确定了几种先前未与人类对UTI的反应相关联的新因子的显著反应,包括白细胞介素(IL)-4、IL-7、IL-9、IL-17A、嗜酸性粒细胞趋化因子、粒细胞巨噬细胞集落刺激因子(GM-CSF)和几种生长因子。这些数据在人类对UPEC的免疫反应与小鼠模型UTI研究之间建立了关键的相似之处,并强调了人类对UPEC免疫反应的复杂性但定义不明确的性质,特别是在急性膀胱炎症状出现后的即刻阶段。