Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract

Spencer, John David; Schwaderer, Andrew L.; Wang, Huanyu; Bartz, Julianne; Kline, Jennifer; Eichler, Tad; DeSouza, Kristin R.; Sims‐Lucas, Sunder; Baker, Peter B.; Hains, David S.

doi:10.1038/ki.2012.410

Cited by 105 publications

(144 citation statements)

References 34 publications

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“…It is seen as early as 30 minutes after infection starts, and levels increase over time. Antimicrobial activity of RNase 6 is the same as RNase 7 [20,21].…”

Section: Antimicrobial Peptidesmentioning

confidence: 70%

Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

Reygaert¹

2014

J Clin Cell Immunol

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The innate immune system responds in a rapid, initially nonspecific manner to infection in the urinary tract. There are many molecules and cells involved in this response. These include: antimicrobial peptides, toll-like receptors, chemokines, cytokines, and neutrophils. The most common cause of urinary tract infections (UTIs) are uropathogenic Escherichia coli (UPEC). The innate immune system responds to the presence of flagella, fimbriae, and the lipopolysaccharide outer membrane of these bacteria. Antimicrobial peptides are used to lyse the bacteria and also prevent the bacteria from binding to epithelial cells in the urinary tract. The toll-like receptors sense the presence of the bacteria and signal for the production of molecules that cause immune and inflammation responses. The various chemokines and cytokines such as CXCL8, CCL2, interleukins (IL-6, IL-8, IL-10, IL-17A), and granulocyte colony stimulating factor (G-CSF), are used for much of the signaling in innate immunity. In addition, neutrophils play a major role in rapid removal of invading bacteria. The rapid innate immune response is designed to remove most of the bacteria within 24 hours in an uncomplicated UTI. This review presents an overview of the innate immune response to UTIs caused by UPEC and the host molecules and cells involved.

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“…It is seen as early as 30 minutes after infection starts, and levels increase over time. Antimicrobial activity of RNase 6 is the same as RNase 7 [20,21].…”

Section: Antimicrobial Peptidesmentioning

confidence: 70%

Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

Reygaert¹

2014

J Clin Cell Immunol

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“…RNase 7 was initially found in epidermis and subsequently found in bladder, ureter and kidney [72,73]. Concentration of RNase 7 is higher than other AMPs and shows sufficient bactericidal effect.…”

Section: Ribonucleasementioning

confidence: 99%

“…Concentration of RNase 7 is higher than other AMPs and shows sufficient bactericidal effect. Rapid and strong action of RNase 7 from Gram positive and negative bacteria results from distraction of cell membrane, that is independent with ribonuclease activity [73]. Antimicrobial processes of RNase 7 are not fully identified.…”

Section: Ribonucleasementioning

confidence: 99%

Molecular Defense Mechanisms during Urinary Tract Infection

Choi

Chang

2015

Urogenit Tract Infect

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The urinary tract is a common site of infection. The complete mechanisms of urinary tract infection (UTI) are still unknown. In general, the strategies of the uropathogenic Escherichia coli are adherence, motility, iron acquisition, toxin, and evasion of host immunity. Host immune responses play a significant part in defense of UTI. Various antimicrobial peptides (AMPs) including defensins, cathelicidin, hepcidin, ribonuclease 7, lactoferrin, lipocalin, Tamm-Horsfall protein, and secretory leukocyte proteinase inhibitor help to prevent UTI by modulation of innate and adaptive immunity. Toll-like receptors (TLRs) play an important role of microorganism identification in innate immunity. Stimulation of TLRs on the cell membrane by ligand of bacteria triggers production of inflammatory chemokines, cytokines, and AMPs. These mechanisms are an attempt to defend the urinary tract against UTI. Keywords: Urinary tract infections; Molecular biology INTRODUCTIONUrinary tract infections (UTIs) are one of the most common infections that lead to out-patient and in-patient hospital visits. About 50% of women suffer from a UTI during their lifetime [1]. About 8 million female patients are treated annually for UTI alone in the United States and UTI recurs in about 30% of those who have normal function and anatomy of urinary tract [2]. UTI comprises acute uncomplicated cystitis and acute uncomplicated pyelonephritis. Acute uncomplicated cystitis results in dysuria, frequency, or urgency in healthy and non-pregnant women [3]. The diagnosis is aided by the presence of pyuria in voided urine and positive urine culture of at least 10 3 CFU/ml [3]. Acute uncomplicated pyelonephritis results in fever, costovertebral angle tenderness and flank pain in healthy and non-pregnant women and is similar to cystitis in lower urinary tract symptoms and laboratory analyses [4]. UTIs are commonly classified as uncomplicated and complicated. Complicated UTI occurs in patients with co-morbid illness or anatomic malformations of the urinary tract that can aggravate the risk of infection or therapeutic failure [5]. Complicating factors, for example, include the presence of catheter, obstructive uropathy, pregnancy, urinary stones, diabetes, and male gender. Most of them are main causes of pathogenesis in the host. Meanwhile, bacterial factors in UTI have been studied worldwide for decades with the main focus on Escherichia coli that is the most common pathogen in community acquired UTI [6]. Eighty percent to ninety percent of acute uncomplicated cystitis or acute uncomplicated pyelonephritis correspond to E. coli and the similar explanation applies to most complicated UTIs [7]. E. coli are classified into intestinal E. coli and extraintestinal E. coli. Most in vivo and clinical studies on extraintestinal E. coli related to UTI show that the specific adaptations of uropathogenic E. coli (UPEC)

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“…We (42) have previously characterized ribonuclease 7, a potent antimicrobial peptide with a broad range of activity against uropathogens in the human kidney. Renal ribonuclease 7 expression is limited to ICs, constitutively expressed at baseline, upregulated in response to infection, and secreted into the urine (42,43). ICs have been demonstrated to express other innate immune proteins, including neutrophil gelatinase-associated lipocalin, also known as lipocalin 2 (gene: Lcn2; protein: Ngal), IL-18 (gene: Il18), and human ␣-defensin 5 (15,28,41).…”

mentioning

confidence: 99%

“…Additionally, uropathogenic Escherichia coli (UPEC) preferentially adhere to the luminal surface of medullary ICs (10). ICs are ideally positioned to defend the kidney from ascending urinary tract infections (UTIs) and activate systemic inflammatory responses (42,43).…”

mentioning

confidence: 99%