Skip to main content

Advertisement

SpringerLink
Log in

The innate immune response during urinary tract infection and pyelonephritis

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides—a ubiquitous component of the innate immune response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AMP:

Antimicrobial peptides

DC:

Dendritic cells

HBD1:

Human beta defensin 1

HBD2:

Human beta defensin 2

HD5:

Human alpha-defensin 5

HNP:

Human neutrophil peptides

RNase 7:

Ribonuclease 7

SLPI:

Secretory leukocyte protease inhibitor

THP:

Tamm–Horsfall protein

TLR:

Toll-like receptor

UPEC:

Uropathogenic Escherichia coli

UTI:

Urinary tract infection

VUR:

Vesicoureteral reflux

References

  1. Bachur RG, Harper MB (2001) Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics 108:311–316

    Article  CAS  PubMed  Google Scholar 

  2. Beetz R (2006) May we go on with antibacterial prophylaxis for urinary tract infections? Pediatr Nephrol 21:5–13

    Article  CAS  PubMed  Google Scholar 

  3. Chesney RW, Carpenter MA, Moxey-Mims M, Nyberg L, Greenfield SP, Hoberman A, Keren R, Matthews R, Matoo TK (2008) Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR): background commentary of RIVUR investigators. Pediatrics 122[Suppl 5]:S233–239

    Article  PubMed  Google Scholar 

  4. Freedman AL (2005) Urologic diseases in North America Project: trends in resource utilization for urinary tract infections in children. J Urol 173:949–954

    Article  PubMed  Google Scholar 

  5. Spencer JD, Schwaderer A, McHugh K, Hains DS (2010) Pediatric urinary tract infections: an analysis of hospitalizations, charges, and costs in the USA. Pediatr Nephrol 25:2469–2475

    Article  PubMed  Google Scholar 

  6. Sobel JD (1997) Pathogenesis of urinary tract infection. Role of host defenses. Infect Dis Clin North Am 11:531–549

    Article  CAS  PubMed  Google Scholar 

  7. Brading AF, Turner WH (1994) The unstable bladder: towards a common mechanism. Br J Urol 73:3–8

    Article  CAS  PubMed  Google Scholar 

  8. Asscher AW, Sussman M, Waters WE, Davis RH, Chick S (1966) Urine as a medium for bacterial growth. Lancet 2:1037–1041

    Article  CAS  PubMed  Google Scholar 

  9. Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K, Fitzgerald M, Mueller ER, Schreckenberger P, Dong Q, Nelson DE, Brubaker L (2012) Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol 50:1376–1383

    Article  PubMed Central  PubMed  Google Scholar 

  10. Ragnarsdottir B, Svanborg C (2012) Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: host-pathogen interaction in urinary tract infections. Pediatr Nephrol 27:2017–2029

    Article  PubMed  Google Scholar 

  11. Mulvey MA, Schilling JD, Martinez JJ, Hultgren SJ (2000) Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. Proc Natl Acad Sci USA 97:8829–8835

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Wright KJ, Seed PC, Hultgren SJ (2005) Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization. Infect Immun 73:7657–7668

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ (1998) Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282:1494–1497

    Article  CAS  PubMed  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[Suppl 2]:29–38

    Article  CAS  PubMed  Google Scholar 

  15. Underwood MA, Bevins CL (2010) Defensin-barbed innate immunity: clinical associations in the pediatric population. Pediatrics 125:1237–1247

    Article  PubMed  Google Scholar 

  16. Song J, Abraham SN (2008) Innate and adaptive immune responses in the urinary tract. Eur J Clin Invest 38[Suppl 2]:21–28

    Article  PubMed  Google Scholar 

  17. Backhed F, Soderhall M, Ekman P, Normark S, Richter-Dahlfors A (2001) Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ-and cell-specific expression of Toll-like receptors within the human urinary tract. Cell Microbiol 3:153–158

    Article  CAS  PubMed  Google Scholar 

  18. Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A, Rysz J (2010) The role of Toll-like receptors in renal diseases. Nat Rev Nephrol 6:224–235

    Article  CAS  PubMed  Google Scholar 

  19. Song J, Abraham SN (2008) TLR-mediated immune responses in the urinary tract. Curr Opin Microbiol 11:66–73

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Hagberg L, Hull R, Hull S, McGhee JR, Michalek SM, Svanborg Eden C (1984) Difference in susceptibility to Gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect Immun 46:839–844

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Andersen-Nissen E, Hawn TR, Smith KD, Nachman A, Lampano AE, Uematsu S, Akira S, Aderem A (2007) Cutting edge: Tlr5−/− mice are more susceptible to Escherichia coli urinary tract infection. J Immunol 178:4717–4720

    Article  CAS  PubMed  Google Scholar 

  22. Samuelsson P, Hang L, Wullt B, Irjala H, Svanborg C (2004) Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect Immun 72:3179–3186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Chassin C, Tourneur E, Bens M, Vandewalle A (2011) A role for collecting duct epithelial cells in renal antibacterial defences. Cell Microbiol 13:1107–1113

    Article  CAS  PubMed  Google Scholar 

  24. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303:1522–1526

    Article  CAS  PubMed  Google Scholar 

  25. Scherberich JE, Hartinger A (2008) Impact of Toll-like receptor signalling on urinary tract infection. Int J Antimicrob Agents 31[Suppl 1]:S9–14

    Article  CAS  PubMed  Google Scholar 

  26. 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[Suppl 2]:12–20

    Article  CAS  PubMed  Google Scholar 

  27. Svanborg-Eden C, de Man P, Jodal U, Linder H, Lomberg H (1987) Host parasite interaction in urinary tract infection. Pediatr Nephrol 1:623–631

    Article  CAS  PubMed  Google Scholar 

  28. Ragnarsdottir B, Samuelsson M, Gustafsson MC, 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  CAS  PubMed  Google Scholar 

  29. El-Achkar TM, Plotkin Z, Marcic B, Dagher PC (2007) Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent. Am J Physiol Renal Physiol 293:F1187–1196

    Article  CAS  PubMed  Google Scholar 

  30. Cheng CH, Lee YS, Tsau YK, Lin TY (2011) Genetic polymorphisms and susceptibility to parenchymal renal infection among pediatric patients. Pediatr Infect Dis J 30:309–314

    Article  PubMed  Google Scholar 

  31. Duell BL, Carey AJ, Tan CK, Cui X, Webb RI, Totsika M, Schembri MA, Derrington P, Irving-Rodgers H, Brooks AJ, Cripps AW, Crowley M, Ulett GC (2012) Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection. J Immunol 188:781–792

    Article  CAS  PubMed  Google Scholar 

  32. Hernandez JG, Sunden F, Connolly J, Svanborg C, Wullt B (2011) Genetic control of the variable innate immune response to asymptomatic bacteriuria. PLoS One 6:e28289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Jiang ZD, Okhuysen PC, Guo DC, He R, King TM, DuPont HL, Milewicz DM (2003) Genetic susceptibility to enteroaggregative Escherichia coli diarrhea: polymorphism in the interleukin-8 promotor region. J Infect Dis 188:506–511

    Article  CAS  PubMed  Google Scholar 

  34. Frendeus B, Godaly G, Hang L, Karpman D, Lundstedt AC, Svanborg C (2000) Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J Exp Med 192:881–890

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Lundstedt AC, Leijonhufvud I, Ragnarsdottir B, Karpman D, Andersson B, Svanborg C (2007) Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. J Infect Dis 195:1227–1234

    Article  PubMed  Google Scholar 

  36. Zaffanello M, Malerba G, Cataldi L, Antoniazzi F, Franchini M, Monti E, Fanos V (2010) Genetic risk for recurrent urinary tract infections in humans: a systematic review. J Biomed Biotechnol 2010:321082

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Centi S, Negrisolo S, Stefanic A, Benetti E, Cassar W, Da Dalt L, Rigamonti W, Zucchetta P, Montini G, Murer L, Artifoni L (2010) Upper urinary tract infections are associated with RANTES promoter polymorphism. J Pediatr 157(1038–1040):e1031

    Google Scholar 

  38. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL (2004) Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun 5:641–647

    Article  CAS  PubMed  Google Scholar 

  39. Haraoka M, Hang L, Frendeus B, Godaly G, Burdick M, Strieter R, Svanborg C (1999) Neutrophil recruitment and resistance to urinary tract infection. J Infect Dis 180:1220–1229

    Article  CAS  PubMed  Google Scholar 

  40. Engel D, Dobrindt U, Tittel A, Peters P, Maurer J, Gutgemann I, Kaissling B, Kuziel W, Jung S, Kurts C (2006) Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance. Infect Immun 74:6100–6107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Tittel AP, Heuser C, Ohliger C, Knolle PA, Engel DR, Kurts C (2011) Kidney dendritic cells induce innate immunity against bacterial pyelonephritis. J Am Soc Nephrol 22:1435–1441

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Hopkins WJ, Uehling DT, Balish E (1987) Local and systemic antibody responses accompany spontaneous resolution of experimental cystitis in cynomolgus monkeys. Infect Immun 55:1951–1956

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Hopkins WJ, James LJ, Balish E, Uehling DT (1993) Congenital immunodeficiencies in mice increase susceptibility to urinary tract infection. J Urol 149:922–925

    CAS  PubMed  Google Scholar 

  44. Thumbikat P, Waltenbaugh C, Schaeffer AJ, Klumpp DJ (2006) Antigen-specific responses accelerate bacterial clearance in the bladder. J Immunol 176:3080–3086

    Article  CAS  PubMed  Google Scholar 

  45. Ali AS, Townes CL, Hall J, Pickard RS (2009) Maintaining a sterile urinary tract: the role of antimicrobial peptides. J Urol 182:21–28

    Article  CAS  PubMed  Google Scholar 

  46. Zasloff M (2007) Antimicrobial peptides, innate immunity, and the normally sterile urinary tract. J Am Soc Nephrol 18:2810–2816

    Article  CAS  PubMed  Google Scholar 

  47. Almeida PF, Pokorny A (2009) Mechanisms of antimicrobial, cytolytic, and cell-penetrating peptides: from kinetics to thermodynamics. Biochemistry 48:8083–8093

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Rathinakumar R, Walkenhorst WF, Wimley WC (2009) Broad-spectrum antimicrobial peptides by rational combinatorial design and high-throughput screening: the importance of interfacial activity. J Am Chem Soc 131:7609–7617

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Splith K, Neundorf I (2011) Antimicrobial peptides with cell-penetrating peptide properties and vice versa. Eur Biophys J 40:387–397

    Article  CAS  PubMed  Google Scholar 

  50. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55:27–55

    Article  CAS  PubMed  Google Scholar 

  51. Ohlsson S, Ljungkrantz I, Ohlsson K, Segelmark M, Wieslander J (2001) Novel distribution of the secretory leucocyte proteinase inhibitor in kidney. Mediators Inflamm 10:347–350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Lehrer RI, Lichtenstein AK, Ganz T (1993) Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol 11:105–128

    Article  CAS  PubMed  Google Scholar 

  53. Liu L, Zhao C, Heng HH, Ganz T (1997) The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics 43:316–320

    Article  CAS  PubMed  Google Scholar 

  54. Linzmeier RM, Ganz T (2005) Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22–p23. Genomics 86:423–430

    Article  CAS  PubMed  Google Scholar 

  55. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3:710–720

    Article  CAS  PubMed  Google Scholar 

  56. Ihi T, Nakazato M, Mukae H, Matsukura S (1997) Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis 25:1134–1140

    Article  CAS  PubMed  Google Scholar 

  57. Tikhonov I, Rebenok A, Chyzh A (1997) A study of interleukin-8 and defensins in urine and plasma of patients with pyelonephritis and glomerulonephritis. Nephrol Dial Transplant 12:2557–2561

    Article  CAS  PubMed  Google Scholar 

  58. Bevins CL (2006) Paneth cell defensins: key effector molecules of innate immunity. Biochem Soc Trans 34:263–266

    Article  CAS  PubMed  Google Scholar 

  59. Porter E, Yang H, Yavagal S, Preza GC, Murillo O, Lima H, Greene S, Mahoozi L, Klein-Patel M, Diamond G, Gulati S, Ganz T, Rice PA, Quayle AJ (2005) Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions. Infect Immun 73:4823–4833

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC (1998) Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247–1258

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Dugan AS, Maginnis MS, Jordan JA, Gasparovic ML, Manley K, Page R, Williams G, Porter E, O’Hara BA, Atwood WJ (2008) Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J Biol Chem 283:31125–31132

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Smith JG, Nemerow GR (2008) Mechanism of adenovirus neutralization by Human alpha-defensins. Cell Host Microbe 3:11–19

    Article  CAS  PubMed  Google Scholar 

  63. Spencer JD, Hains DS, Porter E, Bevins CL, Dirosario J, Becknell B, Wang H, Schwaderer AL (2012) Human alpha defensin 5 expression in the human kidney and urinary tract. PLoS One 7:e31712

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Porter EM, Poles MA, Lee JS, Naitoh J, Bevins CL, Ganz T (1998) Isolation of human intestinal defensins from ileal neobladder urine. FEBS Lett 434:272–276

    Article  CAS  PubMed  Google Scholar 

  65. Townes CL, Ali A, Robson W, Pickard R, Hall J (2011) Tolerance of bacteriuria after urinary diversion is linked to antimicrobial peptide activity. Urology 77(509):e501–508

    Google Scholar 

  66. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469:419–423

    Article  CAS  PubMed  Google Scholar 

  68. Morrison G, Kilanowski F, Davidson D, Dorin J (2002) Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 70:3053–3060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Lehmann J, Retz M, Harder J, Krams M, Kellner U, Hartmann J, Hohgrawe K, Raffenberg U, Gerber M, Loch T, Weichert-Jacobsen K, Stockle M (2002) Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection. BMC Infect Dis 2:20

    Article  PubMed Central  PubMed  Google Scholar 

  70. Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L, Ehren I, Hokfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (2006) The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12:636–641

    Article  CAS  PubMed  Google Scholar 

  71. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781

    Article  CAS  PubMed  Google Scholar 

  72. Park CH, Valore EV, Waring AJ, Ganz T (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810

    Article  CAS  PubMed  Google Scholar 

  73. Wang H, Schwaderer AL, Kline J, Spencer JD, Kline D, Hains DS (2012) Contribution of Structural Domains to Ribonuclease 7’s Activity Against Uropathogenic Bacteria. Antimicrob Agents Chemother 57:766–774

    Article  PubMed  Google Scholar 

  74. Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, Desouza KR, Sims-Lucas S, Baker P, Hains DS (2013) Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int 83:615–625

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Spencer JD, Schwaderer AL, Dirosario JD, McHugh KM, McGillivary G, Justice SS, Carpenter AR, Baker PB, Harder J, Hains DS (2011) Ribonuclease 7 is a potent antimicrobial peptide within the human urinary tract. Kidney Int 80:174–180

    Article  CAS  PubMed  Google Scholar 

  76. Harder J, Schroder JM (2002) RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 277:46779–46784

    Article  CAS  PubMed  Google Scholar 

  77. Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD (2007) The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem 282:4626–4633

    Article  CAS  PubMed  Google Scholar 

  78. Wang H, Schwaderer AL, Kline J, Spencer JD, Kline D, Hains DS (2013) Contribution of Structural Domains to the Activity of Ribonuclease 7 against Uropathogenic Bacteria. Antimicrob Agents Chemother 57:766–774

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Boix E, Nogues MV (2007) Mammalian antimicrobial proteins and peptides: overview on the RNase A superfamily members involved in innate host defence. Mol Biosyst 3:317–335

    Article  CAS  PubMed  Google Scholar 

  80. Reinhart HH, Spencer JR, Zaki NF, Sobel JD (1992) Quantitation of urinary Tamm-Horsfall protein in children with urinary tract infection. Eur Urol 22:194–199

    CAS  PubMed  Google Scholar 

  81. Svanborg-Eden C, Svennerholm AM (1978) Secretory immunoglobulin A and G antibodies prevent adhesion of Escherichia coli to human urinary tract epithelial cells. Infect Immun 22:790–797

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

JDS is supported by the National Institute of Health Grant K08 DK094970-01. ALS and DSH are supported by the National Institute of Health Grant 1RC4DK090937-01.

Disclosure

All of the authors declare no competing interests.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Nephrology, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA

    John David Spencer, Andrew L. Schwaderer, Brian Becknell & David S. Hains

  2. Center for Clinical and Translational Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    John David Spencer, Andrew L. Schwaderer, Brian Becknell & David S. Hains

  3. Kidney Innate Immunity Research Group, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    John David Spencer, Andrew L. Schwaderer, Brian Becknell & David S. Hains

  4. Department of Pediatrics, Division of Infectious Disease, Nationwide Children’s Hospital, Columbus, OH, USA

    Joshua Watson

Authors
  1. John David Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew L. Schwaderer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian Becknell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joshua Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David S. Hains
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John David Spencer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spencer, J.D., Schwaderer, A.L., Becknell, B. et al. The innate immune response during urinary tract infection and pyelonephritis. Pediatr Nephrol 29, 1139–1149 (2014). https://doi.org/10.1007/s00467-013-2513-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-013-2513-9

Keywords

Search

Navigation