Journal List > Urogenit Tract Infect > v.10(2) > 1084185

Choi and Chang: Molecular Defense Mechanisms during Urinary Tract Infection

Abstract

The urinary tract is a common site of infection. The complete mechanisms of urinary tract infection (UTI) are still unknown. In general, the strategies of the uropathogenic Escherichia coli are adherence, motility, iron acquisition, toxin, and evasion of host immunity. Host immune responses play a significant part in defense of UTI. Various antimicrobial peptides (AMPs) including defensins, cathelicidin, hepcidin, ribonuclease 7, lactoferrin, lipocalin, Tamm-Horsfall protein, and secretory leukocyte proteinase inhibitor help to prevent UTI by modulation of innate and adaptive immunity. Toll-like receptors (TLRs) play an important role of microorganism identification in innate immunity. Stimulation of TLRs on the cell membrane by ligand of bacteria triggers production of inflammatory chemokines, cytokines, and AMPs. These mechanisms are an attempt to defend the urinary tract against UTI.

REFERENCES

1.Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003. 49:53–70.
crossref
2.Finer G., Landau D. Pathogenesis of urinary tract infections with normal female anatomy. Lancet Infect Dis. 2004. 4:631–5.
crossref
3.Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am. 2003. 17:303–32.
crossref
4.Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012. 366:1028–37.
5.Nicolle LE. AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005. 16:349–60.
crossref
6.Ragnarsdottir B., Svanborg C. Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: host-pathogen interaction in urinary tract infections. Pediatr Nephrol. 2012. 27:2017–29.
crossref
7.Hooton TM., Scholes D., Hughes JP., Winter C., Roberts PL., Stapleton AE, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med. 1996. 335:468–74.
crossref
8.Stapleton AE. Urinary tract infection in women: new pathogenic considerations. Curr Infect Dis Rep. 2006. 8:465–72.
crossref
9.Lidin-Janson G., Hanson LA., Kaijser B., Lincoln K., Lindberg U., Olling S, et al. Comparison of Escherichia coli from bacteriuric patients with those from feces of healthy schoolchildren. J Infect Dis. 1977. 136:346–53.
10.Welch RA., Burland V., Plunkett G 3rd., Redford P., Roesch P., Rasko D, et al. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2002. 99:17020–4.
crossref
11.Roos V., Schembri MA., Ulett GC., Klemm P. Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae. Microbiology. 2006. 152:1799–806.
crossref
12.Eden CS., Hanson LA., Jodal U., Lindberg U., Akerlund AS. Variable adherence to normal human urinary-tract epithelial cells of Escherichia coli strains associated with various forms of urinary-tract infection. Lancet. 1976. 1:490–2.
13.Cirl C., Wieser A., Yadav M., Duerr S., Schubert S., Fischer H, et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med. 2008. 14:399–406.
crossref
14.Nielubowicz GR., Mobley HL. Host-pathogen interactions in urinary tract infection. Nat Rev Urol. 2010. 7:430–41.
crossref
15.Baorto DM., Gao Z., Malaviya R., Dustin ML., van der Merwe A., Lublin DM, et al. Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature. 1997. 389:636–9.
crossref
16.Schwartz DJ., Kalas V., Pinkner JS., Chen SL., Spaulding CN., Dodson KW, et al. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci U S A. 2013. 110:15530–7.
crossref
17.Leffler H., Svanborg-Eden C. Glycolipid receptors for uropathogenic Escherichia coli on human erythrocytes and uroepithelial cells. Infect Immun. 1981. 34:920–9.
crossref
18.Bergsten G., Samuelsson M., Wullt B., Leijonhufvud I., Fischer H., Svanborg C. PapG-dependent adherence breaks mucosal inertia and triggers the innate host response. J Infect Dis. 2004. 189:1734–42.
crossref
19.Pere A., Nowicki B., Saxen H., Siitonen A., Korhonen TK. Expression of P, type-1, and type-1C fimbriae of Escherichia coli in the urine of patients with acute urinary tract infection. J Infect Dis. 1987. 156:567–74.
20.Goluszko P., Moseley SL., Truong LD., Kaul A., Williford JR., Selvarangan R, et al. Development of experimental model of chronic pyelonephritis with Escherichia coli O75: K5: H-bearing Dr fimbriae: mutation in the dra region prevented tubulointerstitial nephritis. J Clin Invest. 1997. 99:1662–72.
21.Buckles EL., Bahrani-Mougeot FK., Molina A., Lockatell CV., Johnson DE., Drachenberg CB, et al. Identification and characterization of a novel uropathogenic Escherichia coli-associated fimbrial gene cluster. Infect Immun. 2004. 72:3890–901.
22.Valle J., Mabbett AN., Ulett GC., Toledo-Arana A., Wecker K., Totsika M, et al. UpaG, a new member of the trimeric autotransporter family of adhesins in uropathogenic Escherichia coli. J Bacteriol. 2008. 190:4147–61.
23.Lane MC., Lockatell V., Monterosso G., Lamphier D., Weinert J., Hebel JR, et al. Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract. Infect Immun. 2005. 73:7644–56.
24.Snyder JA., Haugen BJ., Buckles EL., Lockatell CV., Johnson DE., Donnenberg MS, et al. Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect Immun. 2004. 72:6373–81.
25.Lane MC., Alteri CJ., Smith SN., Mobley HL. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc Natl Acad Sci U S A. 2007. 104:16669–74.
crossref
26.Hagan EC., Mobley HL. Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection. Mol Microbiol. 2009. 71:79–91.
27.Sabri M., Houle S., Dozois CM. Roles of the extraintestinal pathogenic Escherichia coli ZnuACB and ZupT zinc transporters during urinary tract infection. Infect Immun. 2009. 77:1155–64.
28.Henderson IR., Navarro-Garcia F., Desvaux M., Fernandez RC., Ala'Aldeen D. Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev. 2004. 68:692–744.
crossref
29.Danese PN., Pratt LA., Dove SL., Kolter R. The outer membrane protein, antigen 43, mediates cell-to-cell interactions within Escherichia coli biofilms. Mol Microbiol. 2000. 37:424–32.
crossref
30.Allsopp LP., Beloin C., Moriel DG., Totsika M., Ghigo JM., Schembri MA. Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli. J Bacteriol. 2012. 194:5769–82.
crossref
31.Boehm DF., Welch RA., Snyder IS. Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes. Infect Immun. 1990. 58:1951–8.
crossref
32.Trifillis AL., Donnenberg MS., Cui X., Russell RG., Utsalo SJ., Mobley HL, et al. Binding to and killing of human renal epithelial cells by hemolytic P-fimbriated E. coli. Kidney Int. 1994. 46:1083–91.
33.Smith YC., Rasmussen SB., Grande KK., Conran RM., O'Brien AD. Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice. Infect Immun. 2008. 76:2978–90.
34.Boquet P. The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. Toxicon. 2001. 39:1673–80.
crossref
35.Mills M., Meysick KC., O'Brien AD. Cytotoxic necrotizing factor type 1 of uropathogenic Escherichia coli kills cultured human uroepithelial 5637 cells by an apoptotic mechanism. Infect Immun. 2000. 68:5869–80.
36.Rippere-Lampe KE., O'Brien AD., Conran R., Lockman HA. Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf(1)) attenuates the virulence of uropathogenic Escherichia coli. Infect Immun. 2001. 69:3954–64.
37.Wiles TJ., Bower JM., Redd MJ., Mulvey MA. Use of zebrafish to probe the divergent virulence potentials and toxin requirements of extraintestinal pathogenic Escherichia coli. PLoS Pathog. 2009. 5:e1000697.
crossref
38.Guyer DM., Radulovic S., Jones FE., Mobley HL. Sat, the secreted autotransporter toxin of uropathogenic Escherichia coli, is a vacuolating cytotoxin for bladder and kidney epithelial cells. Infect Immun. 2002. 70:4539–46.
39.Heimer SR., Rasko DA., Lockatell CV., Johnson DE., Mobley HL. Autotransporter genes pic and tsh are associated with Escherichia coli strains that cause acute pyelonephritis and are expressed during urinary tract infection. Infect Immun. 2004. 72:593–7.
40.Goetz DH., Holmes MA., Borregaard N., Bluhm ME., Raymond KN., Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002. 10:1033–43.
crossref
41.Smith KD. Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster. Int J Biochem Cell Biol. 2007. 39:1776–80.
crossref
42.Lloyd AL., Smith SN., Eaton KA., Mobley HL. Uropathogenic Escherichia coli Suppresses the host inflammatory response via pathogenicity island genes sisA and sisB. Infect Immun. 2009. 77:5322–33.
43.Ali AS., Townes CL., Hall J., Pickard RS. Maintaining a sterile urinary tract: the role of antimicrobial peptides. J Urol. 2009. 182:21–8.
crossref
44.Almeida PF., Pokorny A. Mechanisms of antimicrobial, cytolytic, and cell-penetrating peptides: from kinetics to thermodynamics. Biochemistry. 2009. 48:8083–93.
crossref
45.Zasloff M. Antimicrobial peptides, innate immunity, and the normally sterile urinary tract. J Am Soc Nephrol. 2007. 18:2810–6.
46.Splith K., Neundorf I. Antimicrobial peptides with cell- penetrating peptide properties and vice versa. Eur Biophys J. 2011. 40:387–97.
47.Yeaman MR., Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003. 55:27–55.
crossref
48.Lehrer RI., Lichtenstein AK., Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993. 11:105–28.
crossref
49.Liu L., Zhao C., Heng HH., Ganz T. 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. 1997. 43:316–20.
50.Linzmeier RM., Ganz T. Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23. Genomics. 2005. 86:423–30.
51.Selsted ME., Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005. 6:551–7.
crossref
52.Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003. 3:710–20.
crossref
53.Ihi T., Nakazato M., Mukae H., Matsukura S. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis. 1997. 25:1134–40.
crossref
54.Tikhonov I., Rebenok A., Chyzh A. A study of interleukin-8 and defensins in urine and plasma of patients with pyelonephritis and glomerulonephritis. Nephrol Dial Transplant. 1997. 12:2557–61.
crossref
55.Bevins CL. Paneth cell defensins: key effector molecules of innate immunity. Biochem Soc Trans. 2006. 34:263–6.
crossref
56.Dugan AS., Maginnis MS., Jordan JA., Gasparovic ML., Manley K., Page R, et al. Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J Biol Chem. 2008. 283:31125–32.
57.Smith JG., Nemerow GR. Mechanism of adenovirus neutralization by Human alpha-defensins. Cell Host Microbe. 2008. 3:11–9.
58.Furci L., Baldan R., Bianchini V., Trovato A., Ossi C., Cichero P, et al. New role for human -defensin 5 in the fight against hypervirulent Clostridium difficile strains. Infect Immun. 2015. 83:986–95.
crossref
59.Spencer JD., Hains DS., Porter E., Bevins CL., DiRosario J., Becknell B, et al. Human alpha defensin 5 expression in the human kidney and urinary tract. PLoS One. 2012. 7:e31712.
crossref
60.MacRedmond R., Greene C., Taggart CC., McElvaney N., O'Neill S. Respiratory epithelial cells require Toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide. Respir Res. 2005. 6:116.
crossref
61.Valore EV., Park CH., Quayle AJ., Wiles KR., McCray PB Jr., Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest. 1998. 101:1633–42.
crossref
62.Schroeder BO., Wu Z., Nuding S., Groscurth S., Marcinowski M., Beisner J, et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human -defensin 1. Nature. 2011. 469:419–23.
crossref
63.Chen X., Niyonsaba F., Ushio H., Hara M., Yokoi H., Matsumoto K, et al. Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol. 2007. 37:434–44.
64.Fattorini L., Iona E., Ricci ML., Thoresen OF., Orru G., Oggioni MR, et al. Activity of 16 antimicrobial agents against drug- resistant strains of Mycobacterium tuberculosis. Microb Drug Resist. 1999. 5:265–70.
65.Agerberth B., Charo J., Werr J., Olsson B., Idali F., Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000. 96:3086–93.
66.Woo JS., Jeong JY., Hwang YJ., Chae SW., Hwang SJ., Lee HM. Expression of cathelicidin in human salivary glands. Arch Otolaryngol Head Neck Surg. 2003. 129:211–4.
crossref
67.Kai-Larsen Y., Agerberth B. The role of the multifunctional peptide LL-37 in host defense. Front Biosci. 2008. 13:3760–7.
crossref
68.Chromek M., Slamova Z., Bergman P., Kovacs L., Podracka L., Ehren I, et al. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med. 2006. 12:636–41.
crossref
69.Crack LR., Jones L., Malavige GN., Patel V., Ogg GS. Human antimicrobial peptides LL-37 and human -defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus. Clin Exp Dermatol. 2012. 37:534–43.
crossref
70.Weinstein DA., Roy CN., Fleming MD., Loda MF., Wolfsdorf JI., Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 2002. 100:3776–81.
crossref
71.Park CH., Valore EV., Waring AJ., Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001. 276:7806–10.
crossref
72.Harder J., Schroder JM. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem. 2002. 277:46779–84.
crossref
73.Spencer JD., Schwaderer AL., Wang H., Bartz J., Kline J., Eichler T, et al. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int. 2013. 83:615–25.
crossref
74.Abrink M., Larsson E., Gobl A., Hellman L. Expression of lactoferrin in the kidney: implications for innate immunity and iron metabolism. Kidney Int. 2000. 57:2004–10.
75.Flo TH., Smith KD., Sato S., Rodriguez DJ., Holmes MA., Strong RK, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004. 432:917–21.
crossref
76.Berger T., Togawa A., Duncan GS., Elia AJ., You-Ten A., Wakeham A, et al. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2006. 103:1834–9.
crossref
77.Reinhart HH., Spencer JR., Zaki NF., Sobel JD. Quantitation of urinary Tamm-Horsfall protein in children with urinary tract infection. Eur Urol. 1992. 22:194–9.
78.Ohlsson S., Ljungkrantz I., Ohlsson K., Segelmark M., Wieslander J. Novel distribution of the secretory leucocyte proteinase inhibitor in kidney. Mediators Inflamm. 2001. 10:347–50.
crossref
79.Hiemstra PS., Maassen RJ., Stolk J., Heinzel-Wieland R., Steffens GJ., Dijkman JH. Antibacterial activity of antileukoprotease. Infect Immun. 1996. 64:4520–4.
crossref
80.Haversen LA., Engberg I., Baltzer L., Dolphin G., Hanson LA., Mattsby-Baltzer I. Human lactoferrin and peptides derived from a surface-exposed helical region reduce experimental Escherichia coli urinary tract infection in mice. Infect Immun. 2000. 68:5816–23.
81.Choi SY., Kim SJ., Chi BH., Kwon JK., Chang IH. Modulating the internalization of bacille Calmette-Guerin by cathelicidin in bladder cancer cells. Urology. 2015. 85:964.
82.Hertting O., Holm A., Luthje P., Brauner H., Dyrdak R., Jonasson AF, et al. Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder. PLoS One. 2010. 5:e15580.
crossref
83.Rivas-Santiago CE., Rivas-Santiago B., Leon DA., Castaneda-Delgado J., Hernandez Pando R. Induction of -defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis. Clin Exp Immunol. 2011. 164:80–9.
crossref
84.Schwab M., Reynders V., Shastri Y., Loitsch S., Stein J., Schroder O. Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells. Mol Immunol. 2007. 44:2107–14.
crossref
85.Luthje P., Hirschberg AL., Brauner A. Estrogenic action on innate defense mechanisms in the urinary tract. Maturitas. 2014. 77:32–6.
crossref
86.Brancatisano FL., Maisetta G., Di Luca M., Esin S., Bottai D., Bizzarri R, et al. Inhibitory effect of the human liver-derived antimicrobial peptide hepcidin 20 on biofilms of polysaccharide intercellular adhesin (PIA)-positive and PIA-negative strains of Staphylococcus epidermidis. Biofouling. 2014. 30:435–46.
87.Minardi D., Ghiselli R., Cirioni O., Giacometti A., Kamysz W., Orlando F, et al. The antimicrobial peptide tachyplesin III coated alone and in combination with intraperitoneal piperacillin-tazobactam prevents ureteral stent Pseudomonas infection in a rat subcutaneous pouch model. Peptides. 2007. 28:2293–8.
crossref
88.Gao G., Lange D., Hilpert K., Kindrachuk J., Zou Y., Cheng JT, et al. The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials. 2011. 32:3899–909.
crossref
89.Song J., Abraham SN. TLR-mediated immune responses in the urinary tract. Curr Opin Microbiol. 2008. 11:66–73.
crossref
90.Tsuboi N., Yoshikai Y., Matsuo S., Kikuchi T., Iwami K., Nagai Y, et al. Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol. 2002. 169:2026–33.
crossref
91.Hung CC., Chang CT., Chen KH., Tian YC., Wu MS., Pan MJ, et al. Upregulation of chemokine CXCL1/KC by leptospiral membrane lipoprotein preparation in renal tubule epithelial cells. Kidney Int. 2006. 69:1814–22.
crossref
92.Chassin C., Goujon JM., Darche S., du Merle L., Bens M., Cluzeaud F, et al. Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. J Immunol. 2006. 177:4773–84.
93.Andersen-Nissen E., Hawn TR., Smith KD., Nachman A., Lampano AE., Uematsu S, et al. Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection. J Immunol. 2007. 178:4717–20.
94.Hayashi T., Crain B., Corr M., Chan M., Cottam HB., Maj R, et al. Intravesical Toll-like receptor 7 agonist R-837: optimization of its formulation in an orthotopic mouse model of bladder cancer. Int J Urol. 2010. 17:483–90.
crossref
95.Andreoni G., Curatolo D., Rocchi G., Rosti U., Velli V. Multiplication of Toxoplasma gondii strain RH in cellular cultures of human amnion and of monkey kidney. Minerva Ginecol. 1965. 17:785–7.
96.Zhang D., Zhang G., Hayden MS., Greenblatt MB., Bussey C., Flavell RA, et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004. 303:1522–6.
crossref
97.Gluba A., Banach M., Hannam S., Mikhailidis DP., Sakowicz A., Rysz J. The role of Toll-like receptors in renal diseases. Nat Rev Nephrol. 2010. 6:224–35.
crossref
98.Thumbikat P., Waltenbaugh C., Schaeffer AJ., Klumpp DJ. Antigen-specific responses accelerate bacterial clearance in the bladder. J Immunol. 2006. 176:3080–6.
crossref
99.Song J., Abraham SN. Innate and adaptive immune responses in the urinary tract. Eur J Clin Invest. 2008. 38(Suppl 2):21–8.
crossref

Table 1.
Virulence factors of uropathogenic Escherichia coli
Classification Virulence factors
Metal acquisition heme, enterobactin, siderophores (Iron), ZnuACB (Zinc)
Toxins Cytotoxic necrotizing factor 1, Sat, Pic, Tsh
Evasion from host defenses Salmochelin, SisA, SisB
Fimbriae Type-1, P, F1c, Dr, Auf, S, M fimbriae
Table 2.
Uropathogenic Escherichia coli fimbrial adhesion binding receptor
Type of fimbriae Binding receptor
Type 1 fimbriae Secretory IgA, UP1A, UP1b, UP2, UP3a, CD11, CD18, CD44, CD48, N-oligosaccharide on integrins 1 and 3, Tamm-Horsfall protein
P fimbriae Glycosphingolipid receptor, -D-galactopyranosyl-(1-4)--D-galactopyranoside receptor
Dr fimbriae Type IV collagen, decay-accelerating factor, CD55
F1C fimbriae Galactosylceramide target (bladder, kidney), globotriaosylceramide (kidney)
S fimbriae Sialic acid glycolipids, glycoproteins, -sialyl-2,3-galactose receptor

IgA: Immunoglobulin A, UP: uroplakin.

Table 3.
Uropathogenic Escherichia coli fimbrial adhesion binding sites in kidney
Human kidney region Type of fimbriae
Vessel walls P, S, type 1, F1C
Glomerulus P, S
Bowman's capsules P, S, Dr
Proximal tubules P, S, type 1, Dr
Distal tubules P, S, type 1, F1C, Dr
Collecting duct P, S, type 1, F1C, Dr
Table 4.
Known antimicrobial peptides (AMPs) in the human kidney and urinary tract
AMPs
Proximal tubule LL-37
Loop of Henle HBD1, HBD2, HD5, LEAP-1, THP
Distal convoluted tubule Collecting Tubule HBD1, lactoferrin, SLPI HBD1, HBD2, HD5, RNase 7
Renal pelvis HD5, RNase 7
Ureter HD5, LL-37, RNase 7
Bladder HD5, RNase 7
Urethra HD5

HBD: human -defensins, HD: human -defensin, LEAP-1: liver expressed antimicrobial peptide-1, THP: Tamm-Horsfall protein, SLPI: secretory leukocyte proteinase inhibitor, RNase 7: ribonuclease 7.

Table 5.
Known Toll-like receptors (TLRs) mainly expressed in urothelium
  Ligand Organism Location
TLR2 Lipoproteins, peptidoglycans, lipoteichoic acid, porins, lipoarabinomannan Gram-positive bacteria, mycobacteria, mycoplasma Cell surface
Phospholipomannans and glucuronoxyl mannans, zymosan, -glucans Fungi  
HSP 70 Human  
TLR3 Double stranded RNA Viruses Cell compartment
TLR4 Lipopolysaccharides Gram-negative bacteria Cell surface
Mannanes Fungi  
HMGB1, HSP, extracellular matrix components Human  
TLR5 Flagellin Flagellated bacteria Cell surface
TLR7 Single stranded RNA RNA viruses Cell compartment
Self DNA/LL-37, self RNA/LL-37 Human  
TLR9 Nonmethylated CpG DNA Bacteria and mycobacteria Cell compartment
DNA Viruses, parasites  
Self DNA/LL-37, self RNA/LL-37, self DNA/HMGB1 Human  
TLR11 (in mice) Profilin Toxoplasma gondii, uropathogenic bacteria Cell compartment

HSP: heat shock protein, HMGB1: high-mobility group protein B1.

TOOLS
Similar articles