Uropathogen and host responses in pyelonephritis

Schwartz, Laura; Ruíz-Rosado, Juan de Dios; Stonebrook, Emily; Becknell, Brian; Spencer, John David

doi:10.1038/s41581-023-00737-6

Cited by 15 publications

(7 citation statements)

References 187 publications

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“…The mammalian collecting ducts possess a diverse repertoire of AMPs that is spatially and temporally expressed during the orchestrated innate response against invasive uropathogens (25,31,58). Because of several potential α-Defensin 1-3-producing cellular sources during UTI, we show that the source of inducible DEFA1A3 expression derives from ICs.…”

Section: Discussionmentioning

confidence: 87%

DEFA1A3DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection

Canas,

Arregui,

Zhang

et al. 2024

Life Sci. Alliance

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Antimicrobial peptides (AMPs) are host defense effectors with potent neutralizing and immunomodulatory functions against invasive pathogens. The AMPs α-Defensin 1-3/DEFA1A3participate in innate immune responses and influence patient outcomes in various diseases. DNA copy-number variations inDEFA1A3have been associated with severity and outcomes in infectious diseases including urinary tract infections (UTIs). Specifically, children with lower DNA copy numbers were more susceptible to UTIs. The mechanism of action by which α-Defensin 1-3/DEFA1A3copy-number variations lead to UTI susceptibility remains to be explored. In this study, we use a previously characterized transgenic knock-in of the humanDEFA1A3gene mouse to dissect α-Defensin 1-3 gene dose–dependent antimicrobial and immunomodulatory roles during uropathogenicEscherichia coli(UPEC) UTI. We elucidate the relationship between kidney neutrophil– and collecting duct intercalated cell–derived α-Defensin 1-3/DEFA1A3expression and UTI. We further describe cooperative effects between α-Defensin 1-3 and other AMPs that potentiate the neutralizing activity against UPEC. Cumulatively, we demonstrate thatDEFA1A3directly protects against UPEC meanwhile impacting pro-inflammatory innate immune responses in a gene dosage–dependent manner.

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Section: Discussionmentioning

confidence: 87%

DEFA1A3DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection

Canas,

Arregui,

Zhang

et al. 2024

Life Sci. Alliance

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“…Bacterial infections have greatly affected the health of people around the world. , As a significant bacterial infectious disease, urinary tract infections (UTIs) can cause urinary frequency or urgency, dysuria, pyelonephritis, and even death. , Particularly, children and postmenopausal women are vulnerable to UTIs. , However, in most patients, bacterial infections are not identified until they reach a systemic stage or present clinical symptoms . Thus, rapid and accurate detection of pathogens is the key to efficient treatment of bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 As a significant bacterial infectious disease, urinary tract infections (UTIs) can cause urinary frequency or urgency, dysuria, pyelonephritis, and even death. 3,4 Particularly, children and postmenopausal women are vulnerable to UTIs. 5,6 However, in most patients, bacterial infections are not identified until they reach a systemic stage or present clinical symptoms.…”

Section: ■ Introductionmentioning

confidence: 99%

Antimicrobial Agent Functional Gold Nanocluster-Mediated Multichannel Sensor Array for Bacteria Sensing

Xiao,

Cheng,

Zhu

et al. 2024

Langmuir

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Urinary tract infections (UTIs) have greatly affected human health in recent years. Accurate and rapid diagnosis of UTIs can enable a more effective treatment. Herein, we developed a multichannel sensor array for efficient identification of bacteria based on three antimicrobial agents (vancomycin, lysozyme, and bacitracin) functional gold nanoclusters (AuNCs). In this sensor, the fluorescence intensity of the three AuNCs was quenched to varying degrees by the bacterial species, providing a unique fingerprint for different bacteria. With this sensing platform, seven pathogenic bacteria, different concentrations of the same bacteria, and even bacterial mixtures were successfully differentiated. Furthermore, UTIs can be accurately identified with our sensors in ∼30 min with 100% classification accuracy. The proposed sensing systems offer a rapid, high-throughput, and reliable sensing platform for the diagnosis of UTIs.

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“…AMPs have been implicated in host defense against UTI, based on their potent antimicrobial activity toward uropathogenic bacteria in vitro, as well as their potential to attenuate host susceptibility to experimental UTI in vivo. Multiple cell types produce AMPs during UTI, including urothelial cells, kidney intercalated cells, neutrophils, monocytes, and macrophages [7,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection

Ruiz-Rosado,

Cortado,

Kercsmar

et al. 2023

J Innate Immun

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Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.

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Uropathogen and host responses in pyelonephritis

Cited by 15 publications

References 187 publications

DEFA1A3DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection

DEFA1A3DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection

Antimicrobial Agent Functional Gold Nanocluster-Mediated Multichannel Sensor Array for Bacteria Sensing

Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection

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