Urinary Tract Infections: Renal Intercalated Cells Protect against Pathogens

Abstract

Urinary tract infections (UTIs) affect more than 1 in 2 women during their lifetime. Among these, more than 10 % of patients carry antibiotic-resistant bacterial strains, highlighting the urgent need to identify alternative treatments. While innate defence mechanisms are well characterized in the lower urinary tract, it is becoming evident that the collecting duct, the first renal segment encountered by invading uropathogenic bacteria, also contributes to bacterial clearance. However, the role of this segment is beginning to be understood. This review summarizes the current knowledge on collecting duct intercalated cells in urinary tract bacterial clearance. Understanding the innate protective role of the uroepithelium and of the collecting duct offers new opportunities for alternative therapeutic strategies.

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

“…Induction of intercalated cell α-Defensin 1-3/DEFA1A3 expression contributes to reduced urinary tract bacterial burden under the UPEC superinfection challenge Because transcription and translation of PMN-derived α-Defensin 1-3/DEFA1A3 occur during promyelocytic stages in the bone marrow, we evaluated the possibility that α-Defensin 1-3 from other cellular sources represent the increased DEFA1A3 mRNA expression in the infected kidney (37,38). Collecting duct epithelial-derived ICs were postulated as the source of DEFA1A3 induction in the kidney because of shared physiology with other constitutive and inducible renal AMPs (22,39,40). After enrichment of kidney-derived PMNs, collecting duct epithelial ICs, and kidney cells that are not intercalated cells (non-ICs), we performed quantification of DEFA1A3 gene expression that reveals the increased mRNA expression of bacterial CFUs in the kidney (r = −0.063), although non-IC mRNA expression increased to a lesser extent than ICs (2.1 ± 0.33 mRNA fold expression) (Figs 1D and S1D and E).…”

“…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. Collecting duct ICs are characterized to perform distal acid-base homeostasis and production of AMPs such as αand β-defensins, cathelicidin, lipocalin, calprotectin, and ribonucleases (11,39,40,59). Non-ICs consist of all the other heterogeneous epithelial, endothelial, and interstitial cells that make up the kidney.…”