Browsing by Author "Zepeda-Orozco, Diana"

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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.