Home LiteratureArticle Details
PMID: 20083670 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 184 ·No. 4 ·2010-02-15 ·Pages 2065-75

Sivick KE, Schaller MA, Smith SN, Mobley HL

Abstract

Uropathogenic Escherichia coli is the causative agent for >80% of uncomplicated urinary tract infections (UTIs). Uropathogenic E. coli strains express a number of virulence and fitness factors that allow successful colonization of the mammalian bladder. To combat this, the host has distinct mechanisms to prevent adherence to the bladder wall and to detect and kill uropathogenic E. coli in the event of colonization. In this study, we investigated the role of IL-17A, an innate-adaptive immunomodulatory cytokine, during UTI using a murine model. Splenocytes isolated from mice infected by the transurethral route robustly expressed IL-17A in response to in vitro stimulation with uropathogenic E. coli Ags. Transcript expression of IL-17A in the bladders of infected mice correlated with a role in the innate immune response to UTI, and gammadelta cells seem to be a key source of IL-17A production. Although IL-17A seems to be dispensable for the generation of a protective response to uropathogenic E. coli, its importance in innate immunity is demonstrated by a defect in acute clearance of uropathogenic E. coli in IL-17A(-/-) mice. This clearance defect is likely a result of deficient cytokine and chemokine transcripts and impaired macrophage and neutrophil influx during infection. These results show that IL-17A is a key mediator for the innate immune response to UTIs.

MeSH Terms
Animals Disease Models, Animal Escherichia coli/immunology,pathogenicity Escherichia coli Infections/immunology,metabolism,microbiology Immunity, Innate Interleukin-17/deficiency,genetics,physiology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Receptors, Antigen, T-Cell, gamma-delta/deficiency,genetics T-Lymphocyte Subsets/immunology,metabolism Urinary Tract Infections/immunology,metabolism,microbiology
Chemicals
Il17a protein, mouse Interleukin-17 Receptors, Antigen, T-Cell, gamma-delta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sivick Kelsey E
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Schaller Matthew A
Smith Sara N
Mobley Harry L T
References (75)
75 references, click to expand
  1. Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum.
    J Exp Med. 2009 Jun 8;206(6):1219-25 PMID: 19468065
  2. Characterization of T-cell receptor gamma delta T cells appearing at the early phase of murine Listeria monocytogenes infection.
    Immunology. 1993 Jan;78(1):22-7 PMID: 8094708
  3. Reaction of the vesical wall to bacterial penetration: resistance to attachment, desquamation, and leukocytic activity.
    Invest Urol. 1977 Nov;15(3):185-93 PMID: 591263
  4. Neutrophil recruitment and resistance to urinary tract infection.
    J Infect Dis. 1999 Oct;180(4):1220-9 PMID: 10479151
  5. [Study on local immune response in Escherichia coli-induced experimental urinary tract infection in mice--infiltration of Ia-positive cells, macrophages, neutrophils, T cells and B cells].
    Kansenshogaku Zasshi. 1992 Jul;66(7):964-73 PMID: 1431374
  6. IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.
    Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G1035-44 PMID: 12016129
  7. Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production.
    J Immunol. 2007 Apr 1;178(7):4466-72 PMID: 17372004
  8. Structural analysis of human beta-defensin-1 and its significance in urinary tract infection.
    Nephron. 2000 May;85(1):34-40 PMID: 10773753
  9. A toll-like receptor that prevents infection by uropathogenic bacteria.
    Science. 2004 Mar 5;303(5663):1522-6 PMID: 15001781
  10. Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection.
    Infect Immun. 2007 Aug;75(8):3941-9 PMID: 17517861
  11. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge.
    J Immunol. 2009 Mar 15;182(6):3469-81 PMID: 19265125
  12. Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection.
    Eur J Clin Invest. 2005 Apr;35(4):227-35 PMID: 15816991
  13. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection.
    J Immunol. 1987 May 15;138(10):3475-80 PMID: 3553327
  14. Diversity, rearrangement, and expression of murine T cell gamma genes.
    Cell. 1986 Jun 6;45(5):733-42 PMID: 3486721
  15. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis.
    J Exp Med. 2009 Feb 16;206(2):299-311 PMID: 19204111
  16. IL-17 signaling for mRNA stabilization does not require TNF receptor-associated factor 6.
    J Immunol. 2009 Feb 1;182(3):1660-6 PMID: 19155515
  17. Urologic diseases in America Project: analytical methods and principal findings.
    J Urol. 2005 Mar;173(3):933-7 PMID: 15711342
  18. Self heat shock and gamma delta T-cell reactivity.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):1767-71 PMID: 2106682
  19. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection.
    J Immunol. 2006 Oct 1;177(7):4662-9 PMID: 16982905
  20. Ordered rearrangement of variable region genes of the T cell receptor gamma locus correlates with transcription of the unrearranged genes.
    J Exp Med. 1993 Mar 1;177(3):729-39 PMID: 8382255
  21. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection.
    Infect Immun. 2007 Jun;75(6):3055-61 PMID: 17403873
  22. Urinary tract infection: self-reported incidence and associated costs.
    Ann Epidemiol. 2000 Nov;10(8):509-15 PMID: 11118930
  23. Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains.
    Infect Immun. 1990 May;58(5):1281-9 PMID: 2182540
  24. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
    Nat Med. 2006 Jun;12(6):636-41 PMID: 16751768
  25. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses.
    Immunity. 2009 Jan 16;30(1):108-19 PMID: 19144317
  26. The macrophage mannose receptor induces IL-17 in response to Candida albicans.
    Cell Host Microbe. 2009 Apr 23;5(4):329-40 PMID: 19380112
  27. Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection.
    J Immunol. 2007 Apr 15;178(8):4717-20 PMID: 17404249
  28. Immune responses of IL-4, IL-5, IL-6 deficient mice.
    Immunol Rev. 1995 Dec;148:45-69 PMID: 8825282
  29. Pathogenic Escherichia coli.
    Nat Rev Microbiol. 2004 Feb;2(2):123-40 PMID: 15040260
  30. IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver.
    J Immunol. 2008 Sep 1;181(5):3456-63 PMID: 18714018
  31. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
    Immunity. 2009 Aug 21;31(2):331-41 PMID: 19682929
  32. G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity.
    Cell Microbiol. 2008 Dec;10(12):2568-78 PMID: 18754853
  33. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses.
    Immunity. 2002 Sep;17(3):375-87 PMID: 12354389
  34. IL-17 enhances chemokine gene expression through mRNA stabilization.
    J Immunol. 2007 Sep 15;179(6):4135-41 PMID: 17785852
  35. Th17 cytokines and mucosal immunity.
    Immunol Rev. 2008 Dec;226:160-71 PMID: 19161423
  36. TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells.
    J Immunol. 2006 Dec 1;177(11):7980-9 PMID: 17114471
  37. Uropathogenic Escherichia coli as a model of host-parasite interaction.
    Curr Opin Microbiol. 2006 Feb;9(1):33-9 PMID: 16406777
  38. Gammadelta T cells: functional plasticity and heterogeneity.
    Nat Rev Immunol. 2002 May;2(5):336-45 PMID: 12033739
  39. Virulence factors in Escherichia coli urinary tract infection.
    Clin Microbiol Rev. 1991 Jan;4(1):80-128 PMID: 1672263
  40. Induction, function and regulation of IL-17-producing T cells.
    Eur J Immunol. 2008 Oct;38(10):2636-49 PMID: 18958872
  41. The molecular basis of T helper 1 and T helper 2 cell differentiation.
    Trends Cell Biol. 2000 Dec;10(12):542-50 PMID: 11121747
  42. Expression of the T cell receptor delta-chain repertoire in mouse lymph node.
    Immunol Cell Biol. 1996 Aug;74(4):313-7 PMID: 8872180
  43. TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.
    Eur J Clin Invest. 2008 Oct;38 Suppl 2:12-20 PMID: 18826477
  44. The role of the epithelial cell in Escherichia coli induced neutrophil migration into the urinary tract.
    Eur Respir J. 1996 Aug;9(8):1713-28 PMID: 8866600
  45. IL-17A-expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis.
    J Immunol. 2009 May 15;182(10):6540-9 PMID: 19414809
  46. Antigen-specific responses accelerate bacterial clearance in the bladder.
    J Immunol. 2006 Mar 1;176(5):3080-6 PMID: 16493067
  47. IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa.
    J Immunol. 2008 Oct 1;181(7):4965-75 PMID: 18802100
  48. Interleukin-8 and the neutrophil response to mucosal gram-negative infection.
    J Clin Invest. 1993 Aug;92(2):780-5 PMID: 8349817
  49. Acute pyelonephritis among adults: cost of illness and considerations for the economic evaluation of therapy.
    Pharmacoeconomics. 2005;23(11):1123-42 PMID: 16277548
  50. Interleukin-17A mediates acquired immunity to pneumococcal colonization.
    PLoS Pathog. 2008 Sep 19;4(9):e1000159 PMID: 18802458
  51. Interleukin-17 family members and inflammation.
    Immunity. 2004 Oct;21(4):467-76 PMID: 15485625
  52. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16669-74 PMID: 17925449
  53. 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. 2006 Nov;74(11):6100-7 PMID: 16966414
  54. Of mice and man: TLR11 (finally) finds profilin.
    Trends Immunol. 2005 Oct;26(10):509-11 PMID: 16111920
  55. Susceptibility of immunodeficient gene-knockout mice to urinary tract infection.
    J Urol. 1999 Jan;161(1):338-41 PMID: 10037434
  56. Recognition by gamma/delta T cells.
    Annu Rev Immunol. 1996;14:511-32 PMID: 8717523
  57. IL-17A is produced by Th17, gammadelta T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance.
    Int Immunol. 2008 Sep;20(9):1129-38 PMID: 18599501
  58. Positive selection of dendritic epidermal gammadelta T cell precursors in the fetal thymus determines expression of skin-homing receptors.
    Immunity. 2004 Jul;21(1):121-31 PMID: 15345225
  59. [Tissue gamma/delta T cells in experimental urinary tract infection relationship between other immuno-competent cells].
    Kansenshogaku Zasshi. 1994 Dec;68(12):1498-511 PMID: 7876672
  60. An overview of IL-17 function and signaling.
    Cytokine. 2008 Sep;43(3):402-7 PMID: 18701318
  61. The urinary tract response to entry of pathogens.
    World J Urol. 1999 Dec;17(6):351-8 PMID: 10654365
  62. A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum.
    J Immunol. 2009 Jul 15;183(2):1291-300 PMID: 19542374
  63. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice.
    J Infect Dis. 2004 Aug 1;190(3):624-31 PMID: 15243941
  64. Induction and effector functions of T(H)17 cells.
    Nature. 2008 Jun 19;453(7198):1051-7 PMID: 18563156
  65. Mucosal immunization with iron receptor antigens protects against urinary tract infection.
    PLoS Pathog. 2009 Sep;5(9):e1000586 PMID: 19806177
  66. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense.
    J Exp Med. 2001 Aug 20;194(4):519-27 PMID: 11514607
  67. Endotoxin-induced shedding of viable uroepithelial cells is an antimicrobial defense mechanism.
    Infect Immun. 1988 Jun;56(6):1615-7 PMID: 3286502
  68. T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes.
    Cell. 1993 Feb 12;72(3):337-48 PMID: 8381716
  69. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection.
    J Immunol. 2007 Mar 15;178(6):3786-96 PMID: 17339477
  70. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.
    Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1283-90 PMID: 16684953
  71. Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection.
    Infect Immun. 2005 Jan;73(1):617-21 PMID: 15618203
  72. Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17.
    J Immunol. 2008 Dec 1;181(11):7891-901 PMID: 19017979
  73. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli.
    Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17020-4 PMID: 12471157
  74. Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa.
    Infect Immun. 2004 Jun;72(6):3179-86 PMID: 15155619
  75. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection.
    J Exp Med. 2009 Feb 16;206(2):313-28 PMID: 19204109
Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.0902386
Published
2010-02-15
Epub
2010-00-18
Pages
2065-75
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2821792
Subset
IM
Grants
NIAID NIH HHS · R01 AI043363 · United States
NIAID NIH HHS · R01 AI043363-12 · United States
NIAID NIH HHS · R56 AI043363 · United States
NIAID NIH HHS · AI043363 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.0902386 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2