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Bactofection with Toll-Like Receptor 4 in a Murine Model of Urinary Tract Infection

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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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References

  1. Foxman B (2002) Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Am J Med 113:5S–13S

    Article  PubMed  Google Scholar 

  2. Good DW, George T, Watts BA (2009) Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes. Am J Physiol Renal Physiol 297:F866–F874

    Article  PubMed  CAS  Google Scholar 

  3. Gupta K, Hooton TM, Stamm WE (2001) Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med 135:41–50

    PubMed  CAS  Google Scholar 

  4. Hu KK, Boyko EJ, Scholes D, Normand E, Chen CL, Grafton J, Fihn SD (2004) Risk factors for urinary tract infections in postmenopausal women. Arch Intern Med 164:989–993

    Article  PubMed  Google Scholar 

  5. Hung CS, Dodson KW, Hultgren SJ (2009) A murine model of urinary tract infection. Nat Protoc 4:1230–1243

    Article  PubMed  CAS  Google Scholar 

  6. Chassin C, Vimont S, Cluzeaud F, Bens M, Goujon JM, Fernandez B, Hertig A, Rondeau E, Arlet G, Hornef MW, Vandewalle A (2008) TLR4 facilitates translocation of bacteria across renal collecting duct cells. J Am Soc Nephrol 19:2364–2374

    Article  PubMed  CAS  Google Scholar 

  7. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145

    Article  PubMed  CAS  Google Scholar 

  8. Munch G, Keis R, Wessels A, Riederer P, Bahner U, Heidland A, Niwa T, Lemke HD, Schinzel R (1997) Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. Eur J Clin Chem Clin Biochem 35:669–677

    PubMed  CAS  Google Scholar 

  9. Nielubowicz GR, Mobley HLT (2010) Host-pathogen interactions in urinary tract infection. Nat Rev Urol 7:430–441

    Article  PubMed  CAS  Google Scholar 

  10. Ohkawa H, Ohishi N, Yagi K (1978) Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19:1053–1057

    PubMed  CAS  Google Scholar 

  11. Palffy R, Gardlik R, Hodosy J, Behuliak M, Resko P, Radvansky J, Celec P (2006) Bacteria in gene therapy: bactofection versus alternative gene therapy. Gene Ther 13:101–105

    Article  PubMed  CAS  Google Scholar 

  12. Ragnarsdottir B, Fischer H, Godaly G, Gronberg-Hernandez J, Gustafsson M, Karpman D, Lundstedt AC, Lutay N, Ramisch S, Svensson ML, Wullt B, Yadav M, Svanborg C (2008) TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. Eur J Clin Invest 38:12–20

    Article  PubMed  CAS  Google Scholar 

  13. Ragnarsdottir B, Samuelsson M, Gustafsson MCU, Leijonhufvud I, Karpman D, Svanborg C (2007) Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J Infect Dis 196:475–484

    Article  PubMed  CAS  Google Scholar 

  14. Weichhart T, Haidinger M, Horl WH, Saemann MD (2008) Current concepts of molecular defence mechanisms operative during urinary tract infection. Eur J Clin Invest 38:29–38

    Article  PubMed  CAS  Google Scholar 

  15. Witko-Sarsat V, Friedlander M, CapeillereBlandin C, NguyenKhoa T, Nguyen NT, Zingraff J, Jungers P, DescampsLatscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  PubMed  CAS  Google Scholar 

  16. Yin XL, Chen L, Liu Y, Yang JL, Ma CQ, Yao ZY, Yang LJ, Wei L, Li MY (2010) Enhancement of the innate immune response of bladder epithelial cells by Astragalus polysaccharides through upregulation of TLR4 expression. Biochem Biophys Res Commun 397:232–238

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by the Slovak Research and Development Agency (SRDA)—grant APVV-0117-07. The authors are grateful to Prof. Ivan Pecháň (1932–2010) for great help in establishing the analysis of oxidative stress markers.

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Authors and Affiliations

  1. Institute of Molecular Biomedicine, Comenius University, Sasinkova 4, 811 08, Bratislava, Slovakia

    Ľubomíra Tóthová, Július Hodosy, Natália Kamodyová & Peter Celec

  2. Department of Molecular Biology, Comenius University, Bratislava, Slovakia

    Ľubomíra Tóthová & Peter Celec

  3. Institute of Physiology, Comenius University, Bratislava, Slovakia

    Július Hodosy

  4. Institute of Pathology, Comenius University, Bratislava, Slovakia

    Pavol Janega

  5. Institute of Normal and Pathological Physiology, Slovak Academy of Science, Bratislava, Slovakia

    Pavol Janega

  6. Institute of Microbiology, Comenius University, Bratislava, Slovakia

    Lívia Slobodníková

  7. Institute of Immunology, Comenius University, Bratislava, Slovakia

    Adriana Liptáková

  8. Department of Nephrology and Institute of Pathology, RWTH University of Aachen, Aachen, Germany

    Peter Boor

  9. Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia

    Peter Boor

  10. Institute of Pathophysiology, Comenius University, Bratislava, Slovakia

    Peter Celec

Authors
  1. Ľubomíra Tóthová
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  2. Július Hodosy
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  3. Natália Kamodyová
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  4. Pavol Janega
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  5. Lívia Slobodníková
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  6. Adriana Liptáková
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  7. Peter Boor
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  8. Peter Celec
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Corresponding author

Correspondence to Peter Celec.

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Tóthová, Ľ., Hodosy, J., Kamodyová, N. et al. Bactofection with Toll-Like Receptor 4 in a Murine Model of Urinary Tract Infection. Curr Microbiol 62, 1739–1742 (2011). https://doi.org/10.1007/s00284-011-9922-4

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  • DOI: https://doi.org/10.1007/s00284-011-9922-4

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