Browsing by Subject "Uropathogenic Escherichia coli"

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    MAP3K7 is an innate immune regulatory gene with increased expression in human and murine kidney intercalated cells following uropathogenic Escherichia coli exposure
    (Wiley, 2022) Saxena, Vijay; Arregui, Samuel; Kamocka, Malgorzata Maria; Hains, David S.; Schwaderer, Andrew; Pediatrics, School of Medicine
    Understanding the mechanisms responsible for the kidney's defense against ascending uropathogen is critical to devise novel treatment strategies against increasingly antibiotic resistant uropathogen. Growing body of evidence indicate Intercalated cells of the kidney as the key innate immune epithelial cells against uropathogen. The aim of this study was to find orthologous and differentially expressed bacterial defense genes in human versus murine intercalated cells. We simultaneously analyzed 84 antibacterial genes in intercalated cells enriched from mouse and human kidney samples. Intercalated cell “reporter mice” were exposed to saline versus uropathogenic Escherichia coli (UPEC) transurethrally for 1 h in vivo, and intercalated cells were flow sorted. Human kidney intercalated cells were enriched from kidney biopsy using magnetic‐activated cell sorting and exposed to UPEC in vitro for 1 h. RT2 antibacterial PCR array was performed. Mitogen‐activated protein kinase kinase kinase 7 (MAP3K7) messenger RNA (mRNA) expression increased in intercalated cells of both humans and mice following UPEC exposure. Intercalated cell MAP3K7 protein expression was defined by immunofluorescence and confocal imaging analysis, was consistent with the increased MAP3K7 mRNA expression profiles defined by PCR. The presence of the orthologous innate immune gene MAP3K7/TAK1 suggests that it may be a key regulator of the intercalated cell antibacterial response and demands further investigation of its role in urinary tract infection pathogenesis.
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    Neutrophil NADPH oxidase promotes bacterial eradication and regulates NF-κB-Mediated inflammation via NRF2 signaling during urinary tract infections
    (Elsevier, 2025) Cotzomi-Ortega, Israel; Rosowski, Emily E.; Wang, Xin; Sanchez-Zamora, Yuriko I.; Lopez-Torres, Jeimy M.; Sanchez-Orellana, Gamaliel; Han, Rachel; Vásquez-Martínez, Gabriela; Andrade, Gabriel Mayoral; Ballash, Gregory; Cortado, Hanna; Li, Birong; Ali, Yusuf; Rascon, Raul; Robledo-Avila, Frank; Partida-Sanchez, Santiago; Pérez-Campos, Eduardo; Olofsson-Sahl, Peter; Zepeda-Orozco, Diana; Spencer, John David; Becknell, Brian; Ruiz-Rosado, Juan de Dios; Pediatrics, School of Medicine
    The precise role of neutrophil-derived reactive oxygen species (ROS) in combating bacterial uropathogens during urinary tract infections (UTI) remains largely unexplored. In this study, we elucidate the antimicrobial significance of NADPH oxidase 2 (NOX2)-derived ROS, as opposed to mitochondrial ROS, in facilitating neutrophil-mediated eradication of uropathogenic Escherichia coli (UPEC), the primary causative agent of UTI. Furthermore, NOX2-derived ROS regulate NF-κB-mediated inflammatory responses in neutrophils against UPEC by inducing the release of nuclear factor erythroid 2-related factor 2 (Nrf2) from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1). Consistently, the absence of NOX2 (Cybb-/-) in mice led to uncontrolled bacterial infection associated with increased NF-κB signaling, heightened neutrophilic inflammation, and increased bladder pathology during cystitis. These findings underscore a dual role for neutrophil NOX2 in both eradicating UPEC and mitigating neutrophil-mediated inflammation in the urinary tract, revealing a previously unrecognized effector and regulatory mechanism in the control of UTI.