Abstract: TH-PO0052
STAT3 Drives Intercalated Cell Phagocytosis of Uropathogenic Escherichia coli and Enhances Urinary Tract Infection (UTI) Susceptibility
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Saxena, Vijay, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Arregui, Samuel, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Hains, David S., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Schwaderer, Andrew L., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Pyelonephritis causes substantial morbidity, mortality, and health care costs, yet kidney innate defense mechanisms remain incompletely understood. We previously showed that human and murine intercalated cells (ICs) produce antimicrobial peptides, phagocytose bacteria, and acidify E. coli bioparticles for clearance (Saxena et al., Nature Communications, 2021; PMID:33893305). These findings support a key role for ICs in kidney innate immunity. Here, we present preliminary evidence that IC phagocytosis of E. coli is dependent on STAT3 signaling.
Methods
Immunofluorescence staining of kidney sections was performed to localize STAT3 and assess colocalization with the IC marker V-ATPase subunit E1 (ATP6V1E1). C57BL/6, C3H/HeN, and C3H/HeOuJ mice were treated with the STAT3 inhibitor STATTIC (20 mg/kg) or DMSO vehicle control for 3 days before transurethral infection with the uropathogenic E. coli strain CFT073 to induce UTI. Renal bacterial burden was quantified by culturing kidney lysates for colony-forming units (CFU). IC phagocytosis of E. coli was assessed by flow cytometry using pHrodo Green E. coli bioparticles. Expression of Atp6v1b1 and Atp6v1g3 mRNA was measured by RT-PCR.
Results
Immunofluorescence of murine kidney sections demonstrated STAT3 localization within ICs. In vivo STAT3 inhibition significantly increased renal bacterial burden across all mouse strains tested: C57BL/6 (mean CFU: 80 control vs. 1953 STATTIC, P=0.010), C3H/HeN (242 vs. 7450, P=0.04), and C3H/HeOuJ (32,223 vs. 101,946, P=0.06). Kidney lysates from STATTIC-treated mice showed reduced phospho-STAT3 levels (26% decrease, P<0.01). In vitro, STATTIC (100 µM) significantly impaired IC phagocytosis of E. coli bioparticles compared with DMSO control (40% vs. 15%, P<0.001).
Conclusion
These findings identify STAT3 signaling as a critical regulator of IC-mediated host defense during UPEC infection. Successful phagocytosis of UPEC by ICs is STAT3-dependent, and pharmacologic inhibition of STAT3 exacerbates pyelonephritis in vivo by increasing renal bacterial burden. Together, these data support a central role for STAT3 in kidney innate immunity and suggest that impaired STAT3 signaling may compromise antibacterial clearance during UTI
Acknowledgment
Supported by NIDDK R01DK136510
Funding
- NIDDK Support