Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.

IF 4.7 3区 医学 Q2 IMMUNOLOGY
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-14 DOI:10.1159/000539177
Hanna Cortado, Macie Kercsmar, Birong Li, Gabriela Vasquez-Martinez, Sudipti Gupta, Christina Ching, Gregory Ballash, Israel Cotzomi-Ortega, Yuriko I Sanchez-Zamora, Ester Boix, Diana Zepeda-Orozco, Ashley R Jackson, John David Spencer, Juan de Dios Ruiz-Rosado, Brian Becknell
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引用次数: 0

Abstract

Introduction: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI.

Methods: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility.

Results: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages.

Conclusion: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

小鼠核糖核酸酶 6 限制了实验性尿路感染过程中的细菌扩散
简介:核糖核酸酶(RNase)A超家族编码的阳离子抗菌蛋白对尿路病原菌具有强大的杀微生物活性。核糖核酸酶 6(RNase6)是一种进化保守的白细胞衍生抗菌肽,对尿路感染(UTI)中最常见的细菌--尿路致病性大肠杆菌(UPEC)具有强大的杀菌活性。在这项研究中,我们产生了 Rnase6 缺乏小鼠,以研究内源性 RNase 6 限制宿主对 UTI 易感性的假设:我们产生了一个 Rnase6EGFP 基因敲入等位基因,以确定 Rnase6 的细胞来源,并确定同源 Rnase6 缺失对抗菌活性和 UTI 易感性的影响:结果:我们确定单核细胞和巨噬细胞是 Rnase6EGFP/+ 小鼠膀胱和肾脏中 Rnase6 的主要细胞来源。与 Rnase6+/+ 对照组相比,Rnase6 缺乏(即 Rnase6EGFP/EGFP)导致实验性 UTI 期间上尿路 UPEC 负担增加。UPEC 在缺乏 Rnase6 的巨噬细胞中的细胞内存活率增加:我们的研究结果证实,RNase6 可通过促进单核细胞和巨噬细胞杀死细胞内的 UPEC 来预防肾盂肾炎,并加强了内源性抗微生物 RNase A 蛋白对宿主 UTI 防御的重要贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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