The immune responses to different Uropathogens call individual interventions for bladder infection

Li, Linlong; Li, Yangyang; Yang, Jiali; Xie, Xue‐Jun; Chen, Huan

doi:10.3389/fimmu.2022.953354

Cited by 8 publications

(6 citation statements)

References 208 publications

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“…Macrophages and mast cells play a key role in immune regulation of the urinary tract, coordinating the recruitment and initiation of neutrophil responses that lead to the removal of bacteria in the bladder. In addition, these cells are critical in preventing an excessive neutrophil response from causing damage to bladder tissue and predisposing this organ to persistent infection [33].…”

Section: Immune Response To Uropathogensmentioning

confidence: 99%

Urinary Tract Infections: The Current Scenario and Future Prospects

Mancuso

Midiri

Gerace³

et al. 2023

Pathogens

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Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, occurring in both community and healthcare settings. Although the clinical symptoms of UTIs are heterogeneous and range from uncomplicated (uUTIs) to complicated (cUTIs), most UTIs are usually treated empirically. Bacteria are the main causative agents of these infections, although more rarely, other microorganisms, such as fungi and some viruses, have been reported to be responsible for UTIs. Uropathogenic Escherichia coli (UPEC) is the most common causative agent for both uUTIs and cUTIs, followed by other pathogenic microorganisms, such as Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus spp. In addition, the incidence of UTIs caused by multidrug resistance (MDR) is increasing, resulting in a significant increase in the spread of antibiotic resistance and the economic burden of these infections. Here, we discuss the various factors associated with UTIs, including the mechanisms of pathogenicity related to the bacteria that cause UTIs and the emergence of increasing resistance in UTI pathogens.

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Section: Immune Response To Uropathogensmentioning

confidence: 99%

Urinary Tract Infections: The Current Scenario and Future Prospects

Mancuso

Midiri

Gerace³

et al. 2023

Pathogens

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“…The uroepithelium and resident innate immune cells in the bladder quickly protect against microbial threats by first identifying microbial patterns and triggering an immune response that produces antimicrobial peptides and pro-inflammatory cytokines [ 17 , 18 , 19 , 20 ]. The biomarkers used in this study [neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β)] are essential components of the constitutive immune response in the urinary tract and have been studied in association with UTIs.…”

Section: Introductionmentioning

confidence: 99%

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Parnell¹,

Luke²,

Mathur³

et al. 2023

Diagnostics

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The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.

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“…[19][20][21] In addition, resident and recruited immune cells secrete pro-inflammatory cytokines, such as interleukins (ILs), including IL-8, also known as chemokine (C-X-C motif) ligand 8 (CXCL8), [17,[22][23][24][25][26] and IL-1β [22,27,28], to further promote the response until the microbial threat is resolved. [17,18,29] Soluble infection-associated biomarkers, such as NGAL, IL-8, and IL-1β, are detectable in urine and studies have demonstrated the association of these urinary biomarkers with the presence of a clinically diagnosed UTI. [16,30,31] Using such biomarkers individually, or in combination, provides strong evidence of immune response to uropathogens in the urinary tract at the time of urine collection.…”

Section: Of 16mentioning

confidence: 99%

Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and Specificity for Detecting UTIs

Akhlaghpour,

Haley,

Parnell

et al. 2023

Preprint

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We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

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The immune responses to different Uropathogens call individual interventions for bladder infection

Cited by 8 publications

References 208 publications

Urinary Tract Infections: The Current Scenario and Future Prospects

Urinary Tract Infections: The Current Scenario and Future Prospects

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and Specificity for Detecting UTIs

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