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Bactofection with Toll-Like Receptor 4 in a Murine Model of Urinary Tract Infection
Authors:?ubomíra Tóthová  Július Hodosy  Natália Kamodyová  Pavol Janega  Lívia Slobodníková  Adriana Liptáková  Peter Boor  Peter Celec
Institution:(1) Institute of Molecular Biomedicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia;(2) Department of Molecular Biology, Comenius University, Bratislava, Slovakia;(3) Institute of Physiology, Comenius University, Bratislava, Slovakia;(4) Institute of Pathology, Comenius University, Bratislava, Slovakia;(5) Institute of Normal and Pathological Physiology, Slovak Academy of Science, Bratislava, Slovakia;(6) Institute of Microbiology, Comenius University, Bratislava, Slovakia;(7) Institute of Immunology, Comenius University, Bratislava, Slovakia;(8) Department of Nephrology and Institute of Pathology, RWTH University of Aachen, Aachen, Germany;(9) Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia;(10) Institute of Pathophysiology, Comenius University, Bratislava, Slovakia;
Abstract:The role of innate immunity in the prevention of urinary tract infection is well-documented. Toll-like receptor 4 (TLR4) is a major determinant of innate immune response. In an animal model of urinary tract infection, bactofection-mediated gene transfer of TLR4 was tested in a preventive approach. Bactofection with TLR4 reduced the colonization with uropathogenic Escherichia coli by 91% in the kidney and by 41% in the bladder. Reduced colonization was associated with lower oxidative stress and expression of monocyte chemoattractant protein-1 and myeloperoxidase in the kidney. Bactofection with TLR4 was successful in the prevention of ascending pyelonephritis. Further studies should focus on long-term effects, the dose response and the potential therapeutic use in models of chronic urinary tract infection.
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