Circulating Neutrophils Exhibit an Altered Immune Response in Chronic LUTS: An Image-Based Deep Learning Analysis

Area of Science:

• Urology
• Immunology
• Microbiology

Background:

• Chronic lower urinary tract symptoms (LUTS) are persistent and linked to elevated urinary leukocytes, suggesting an underlying infection.
• Current diagnostic tests struggle to identify refractory infections, leading to the hypothesis of aberrant neutrophil function in chronic LUTS.

Purpose of the Study:

• To investigate the hypothesis that neutrophils from chronic LUTS patients exhibit an aberrant response preventing complete disease resolution.
• To compare the function of neutrophils from healthy individuals and chronic LUTS patients when exposed to bacteria in different urine conditions.

Main Methods:

• Isolated neutrophils from healthy women and chronic LUTS patients.
• Stimulated neutrophils with commensal and pathogenic E. coli in artificial, control, or patient urine.
• Utilized live imaging for 15 hours to analyze neutrophil viability, morphology, activity, and bacterial growth.

Main Results:

• Neutrophils distinguished between commensal and pathogenic E. coli, with faster death upon pathogenic strain exposure.
• Patient neutrophils exhibited higher activity and delayed death when stimulated with bacteria in control urine.
• Patient neutrophils showed reduced survival in patient urine, even without bacterial stimulation.

Conclusions:

• Neutrophil responses to bacteria are temporally different in chronic LUTS patients.
• Dysregulation in neutrophil maturation or activation may contribute to symptom persistence in chronic LUTS.
• Aberrant neutrophil function impairs bacterial clearance and prolongs symptom duration in chronic LUTS.