Urine Cytokine and Chemokine Levels Predict Urinary Tract Infection Severity Independent of Uropathogen, Urine Bacterial Burden, Host Genetics, and Host Age

Abstract

Urinary tract infections (UTIs) are among the most common infections worldwide. Diagnosing UTIs in older adults poses a significant challenge as asymptomatic colonization is common. Identification of a non-invasive profile that predicts likelihood of progressing from urine colonization to severe disease would provide a significant advantage in clinical practice. We monitored colonization susceptibility, disease severity, and immune response to two uropathogens in two mouse strains across three age groups to identify predictors of infection outcome. caused more severe disease than regardless of mouse strain or age, and was associated with differences in IL-1β, IFN-β, CXCL5 (LIX), CCL5 (RANTES), and CCL2 (MCP-1). In comparing the response to infection across age groups, mature adult mice were better able to control colonization and prevent progression to kidney colonization and bacteremia than young or aged mice, regardless of mouse strain or bacterial species, and this was associated with differences in IL-23, CXCL1, and CCL5. A bimodal distribution was noted for urine colonization, which was strongly associated with bladder CFUs and the magnitude of the immune response but independent of age or disease severity. To determine the value of urine cytokine and chemokine levels for predicting severe disease, all infection datasets were combined and subjected to a series of logistic regressions. A multivariate model incorporating IL-1β, CXCL1, and CCL2 had strong predictive value for identifying mice that did not develop kidney colonization or bacteremia, regardless of mouse genetic background, age, infecting bacterial species, or urine bacterial burden. In conclusion, urine cytokine profiles could potentially serve as a non-invasive decision-support tool in clinical practice and contribute to antimicrobial stewardship.

Androgen-Influenced Polarization of Activin A-Producing Macrophages Accompanies Post-pyelonephritic Renal Scarring

“…Macrophage polarization is also highly dependent on secreted cytokines that are secreted by the injured tissue and the macrophages themselves (27,96). M1 polarization occurs via stimulation with several pro-inflammatory signals (e.g., LPS and IFNγ, with ensuing TNFα, and IL-6 production) (15)(16)(17)(18)(19)(20)(21)(22)(23), as are normally elicited early after bacterial infection of the urinary tract (104)(105)(106). M2 macrophages are sensitive to a variety of Th2 cytokines, including CXCL1, G-CSF and IL-10 (27, 31-33).…”

Urinary tract infections (UTIs) or genital tract infections (GTIs)? It's the diagnostics that count

“…1) and Table 2 (Tab. 2) [ 2 ], [ 3 ], [ 42 ], [ 50 ], [ 51 ], [ 52 ], [ 53 ], [ 54 ], [ 55 ], [ 56 ], [ 57 ], [ 58 ], [ 59 ], [ 60 ], [ 61 ], [ 62 ], [ 63 ], [ 64 ], [ 65 ], [ 66 ], [ 67 ], [ 68 ].…”

“…In toto, the determination of microbial patterns to detect and identify microbial causative agents of UGTIs will be unavoidable in the near future. Thus, microbial biomarkers are our new options to provid high quality detection and identification of UGTIs [ 2 ], [ 3 ], [ 9 ], [ 10 ], [ 16 ], [ 17 ], [ 45 ], [ 68 ], [ 69 ], [ 70 ], [ 71 ].…”

Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine

“…Most of the inflammatory proteins were below detectable range of the assay. The absence of pro-inflammatory proteins in the urine of RC patients is striking, given that inflammatory proteins are elevated in urine samples of patients with other bladder conditions, including interstitial cystitis, bacterial cystitis, bladder cancer, and urinary tract infections [ 6 , 30 , 31 ]. The cytokines IL-1a, IL-6, IL-8 and MIP-1a were detectable in one or two RC patients with gross hematuria and high symptom scores.…”