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Updated: Sep 23, 2026
Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions
Published on: June 13, 2025
Developmental aspects of Escherichia coli-induced innate responses in rat renal epithelial cells
Asa Laestadius1, Tomas Söderblom, Anita Aperia
1Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden. asa.laestadius@ks.se
Insights
Infant kidneys show a weaker IL-6 response to E. coli infection compared to pubertal kidneys. This suggests infant pyelonephritis scarring is due to urinary tract anatomy, not immune immaturity.
Area of Science:
- Pediatric Nephrology
- Infectious Diseases
- Immunology
Background:
- Renal scarring post-pyelonephritis is frequent in infants.
- The innate immune response in infant kidneys to E. coli is not fully understood.
- Alpha-hemolysin-expressing E. coli is a common cause of pediatric urinary tract infections.
Purpose of the Study:
- To compare the renal innate immune response to pyelonephritogenic E. coli in infant and pubertal rats.
- To investigate the role of IL-6 release and Toll-like receptor 4 (TLR4) expression in age-dependent susceptibility to pyelonephritis.
- To determine if immune immaturity contributes to increased pyelonephritic scarring in infants.
Main Methods:
- Experimental study using renal tissue from 10-day-old (infant) and 40-day-old (pubertal) rats.
- Incubation of renal tissue with E. coli supernatant to measure IL-6 release.
- Reverse transcriptase PCR and microdissection to assess TLR4 mRNA expression in renal cortex.
Main Results:
- Basal IL-6 production was lower in infant renal tissue.
- E. coli stimulated a greater fold-increase in IL-6 release in infant tissue, but absolute levels remained lower than in pubertal tissue.
- TLR4 mRNA expression was similar in both age groups and localized to proximal tubules.
Conclusions:
- The innate immune system's IL-6 response is not immature in infants compared to pubertal rats.
- Higher susceptibility to pyelonephritic scarring in infants is unlikely due to immune immaturity.
- Pyelonephritic scarring in infants is likely multifactorial, primarily attributed to urinary tract anatomical immaturity.
Abstract:
Renal scarring after pyelonephritis is common in infancy. In this experimental study performed on tissue from 10-d-old infant and 40-d-old pubertal rats, several aspects of the renal innate immune response to a pyelonephritogenic strain of alpha-hemolysin-expressing Escherichia coli were compared. The kidney typically responds to urinary tract infection with release of proinflammatory cytokines, e.g. IL-6. Basal production of IL-6 from 10-d-old renal cortical tissue was approximately 20% of that from 40-d-old tissue. Six-hour incubation in the presence of supernatant from the E. coli culture caused an approximately 15-fold increase of IL-6 release in 10-d-old tissue and a 5-fold increase in 40-d-old tissue. The absolute level of IL-6 release in stimulated tissue was, however, significantly lower at 10 d than at 40 d. Lipopolysaccharide, the most immunogenic component of E. coli, signals via Toll-like receptor 4. Reverse transcriptase PCR performed on outer renal cortex indicated that expression of Toll-like receptor 4 mRNA was similar in both ages. Microdissection studies revealed that Toll-like receptor 4 mRNA was expressed in proximal tubules but not in glomeruli. The exotoxin alpha-hemolysin, expressed by a majority of uropathogenic E. coli isolates, stimulates IL-6 release via an alternative pathway that signals via intracellular calcium oscillations. We conclude that the higher susceptibility to pyelonephritic scarring is unlikely related to immaturity of innate immune system, as measured by cellular release of IL-6. Instead, the underlying mechanisms for pyelonephritic scarring are most likely multifactorial and may be mainly attributed to anatomic immaturity of the urinary tract.
