TLR-mediated immune responses in the urinary tract

Current Opinion in Microbiology

Volumn 11, Issue 1, 2008, Pages 66-73

  Song, Jeongmin ^a   Abraham, Soman N ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; CHEMOKINE; CYTOKINE; TOLL LIKE RECEPTOR 11; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5;

ANTIBIOTIC THERAPY; BLADDER EPITHELIUM; EPITHELIUM CELL; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; KIDNEY EPITHELIUM; NONHUMAN; REVIEW; URINARY TRACT;

ANIMALS; ENTEROBACTERIACEAE INFECTIONS; HUMANS; TOLL-LIKE RECEPTORS; URINARY TRACT;

EID: 40849087796     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mib.2007.12.001     Document Type: Review

References (43)

1. Hooton T.M., and Stamm W.E. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 11 (1997) 551-581
2. Svanborg C., and Godaly G. Bacterial virulence in urinary tract infection. Infect Dis Clin North Am 11 (1997) 513-529
3. Abraham S.N., Sun D., Dale J.B., and Beachey E.H. Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae. Nature 336 (1988) 682-684
4. Zhou G., Mo W.J., Sebbel P., Min G., Neubert T.A., Glockshuber R., Wu X.R., Sun T.T., and Kong X.P. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci 114 (2001) 4095-4103
5. Andersen-Nissen E., Hawn T.R., Smith K.D., Nachman A., Lampano A.E., Uematsu S., Akira S., and Aderem A. Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection. J Immunol 178 (2007) 4717-4720. Using a murine model of UTI, the authors demonstrate for the first time the importance of TLR5 in regulating innate immune response in the urinary tract. Bladders of wild-type mice showed high levels of cytokine and chemokine expression in response to flagellin, which was linked to increased inflammation and subsequent bacterial clearance.
6. Hagberg L., Hull R., Hull S., McGhee J.R., Michalek S.M., and Svanborg E.C. Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect Immun 46 (1984) 839-844
7. Schilling J.D., Mulvey M.A., Vincent C.D., Lorenz R.G., and Hultgren S.J. Bacterial invasion augments epithelial cytokine responses to Escherichia coli through a lipopolysaccharide-dependent mechanism. J Immunol 166 (2001) 1148-1155
8. Svanborg C., Bergsten G., Fischer H., Godaly G., Gustafsson M., Karpman D., Lundstedt A.C., Ragnarsdottir B., Svensson M., and Wullt B. Uropathogenic Escherichia coli as a model of host-parasite interaction. Curr Opin Microbiol 9 (2006) 33-39
9. Zhang D., Zhang G., Hayden M.S., Greenblatt M.B., Bussey C., Flavell R.A., and Ghosh S. A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303 (2004) 1522-1526
10. Samuelsson P., Hang L., Wullt B., Irjala H., and Svanborg C. Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect Immun 72 (2004) 3179-3186
11. Shahin R.D., Engberg I., Hagberg L., and Svanborg E.C. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J Immunol 138 (1987) 3475-3480
12. Ragnarsdottir B., Samuelsson M., Gustafsson M.C., Leijonhufvud I., Karpman D., and Svanborg C. Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J Infect Dis 196 (2007) 475-484. Human patients afflicted with recurrent bacteriuria are shown to have reduced TLR4 expression in their neutrophils. The inability of these patients to clear UTIs mimics the inability of TLR4 mutant mice to clear UPEC infections. This represents one of the first indications of the contribution of TLR4 in protecting humans against UTIs.
13. Bishop B.L., Duncan M.J., Song J., Li G., Zaas D., and Abraham S.N. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med 13 (2007) 625-630. This paper reveals the underlying mechanism of how UPEC circumvents the bladder barrier by invading and harboring in cAMP-regulatable fusiform vesicles within bladder epithelial cells. The use of forskolin, an inducer of cAMP as a therapeutic agent against UTI is demonstrated.
14. Song J., Bishop B.L., Li G., Duncan M.J., and Abraham S.N. TLR4 initiated and cAMP mediated abrogation of bacterial invasion of the bladder. Cell Host Microbe 1 (2007) 287-298. The authors demonstrate for the first time, the in vivo and in vitro ability of TLR4 to block invasion of BECs by UPEC. They demonstrate that the pathway involves cAMP-mediated inhibition of Rac-1 a critical component of actin rearrangement.
15. Miyazaki J., Kawai K., Oikawa T., Johraku A., Hattori K., Shimazui T., and Akaza H. Uroepithelial cells can directly respond to Mycobacterium bovis bacillus Calmette-Guerin through Toll-like receptor signaling. BJU Int 97 (2006) 860-864
16. Schilling J.D., Martin S.M., Hunstad D.A., Patel K.P., Mulvey M.A., Justice S.S., Lorenz R.G., and Hultgren S.J. CD14- and Toll-like receptor-dependent activation of bladder epithelial cells by lipopolysaccharide and type 1 piliated Escherichia coli. Infect Immun 71 (2003) 1470-1480
17. Chassin C., Goujon J.M., Darche S., du Merle L., Bens M., Cluzeaud F., Werts C., Ogier-Denis E., Le Bouguenec C., Buzoni-Gatel D., et al. Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. J Immunol 177 (2006) 4773-4784
18. Akira S., Uematsu S., and Takeuchi O. Pathogen recognition and innate immunity. Cell 124 (2006) 783-801
19. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., and Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun 61 (1993) 602-609
20. Hang L., Wullt B., Shen Z., Karpman D., and Svanborg C. Cytokine repertoire of epithelial cells lining the human urinary tract. J Urol 159 (1998) 2185-2192
21. 2+.
22. Mulvey M.A., Schilling J.D., Martinez J.J., and Hultgren S.J. Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. Proc Natl Acad Sci U S A 97 (2000) 8829-8835
23. Apodaca G. The uroepithelium: not just a passive barrier. Traffic 5 (2004) 117-128
24. Duncan M.J., Li G., Shin J.S., Carson J.L., and Abraham S.N. Bacterial penetration of bladder epithelium through lipid rafts. J Biol Chem 279 (2004) 18944-18951
25. Duncan M.J., Shin J.S., and Abraham S.N. Microbial entry through caveolae: variations on a theme. Cell Microbiol 4 (2002) 783-791
26. van der Goot F.G., and Harder T. Raft membrane domains: from a liquid-ordered membrane phase to a site of pathogen attack. Semin Immunol 13 (2001) 89-97
27. Eto D.S., Jones T.A., Sundsbak J.L., and Mulvey M.A. Integrin-mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli. PLoS Pathog 3 (2007) e100. A new receptor for UPEC FimH on human bladder epithelial cell lines is described. The functional relevance of this receptor is at present unclear because uroplakin 1a is going to be overwhelmingly expressed in the plasma membrane of superficial BECs. Nevertheless, this finding is important for studies where human epithelial cell lines, which poorly express uroplakin 1a, are used.
28. Echarri A., Muriel O., and Del Pozo M.A. Intracellular trafficking of raft/caveolae domains: insights from integrin signaling. Semin Cell Dev Biol 18 (2007) 627-637
29. Anderson G.G., Palermo J.J., Schilling J.D., Roth R., Heuser J., and Hultgren S.J. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301 (2003) 105-107
30. Justice S.S., Hung C., Theriot J.A., Fletcher D.A., Anderson G.G., Footer M.J., and Hultgren S.J. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci U S A 101 (2004) 1333-1338
31. Justice S.S., Lauer S.R., Hultgren S.J., and Hunstad D.A. Maturation of intracellular Escherichia coli communities requires SurA. Infect Immun 74 (2006) 4793-4800
32. Garofalo C.K., Hooton T.M., Martin S.M., Stamm W.E., Palermo J.J., Gordon J.I., and Hultgren S.J. Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infect Immun 75 (2007) 52-60. A survey of UPEC isolates reveals that over 80% of them can potentially form intracellular bacterial communities.
33. Wright K.J., Seed P.C., and Hultgren S.J. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol 9 (2007) 2230-2241
34. Eto D.S., Sundsbak J.L., and Mulvey M.A. Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli. Cell Microbiol 8 (2006) 704-717
35. Mysorekar I.U., and Hultgren S.J. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci U S A 103 (2006) 14170-14175. In this study, the authors demonstrate that intracellular bacteria can switch into a quiescent phase of growth and that activating these quiescent forms within transitional BECs with cationic compounds can result in resurrection of infection in mice.
36. Gonen E., Vallon-Eberhard A., Elazar S., Harmelin A., Brenner O., Rosenshine I., Jung S., and Shpigel N.Y. Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis. Cell Microbiol 9 (2007) 2826-2838
37. Lane M.C., Alteri C.J., Smith S.N., and Mobley H.L. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc Natl Acad Sci U S A 104 (2007) 16669-16674. Using a biophotonic imaging technique and comparative quantitative PCR, the authors demonstrate the ability of UPEC to tightly regulate expression of flagella in the bladder and kidneys during ascending UTI.
38. Lane M.C., Simms A.N., and Mobley H.L. complex interplay between type 1 fimbrial expression and flagellum-mediated motility of uropathogenic Escherichia coli. J Bacteriol 189 (2007) 5523-5533
39. Billips B.K., Forrestal S.G., Rycyk M.T., Johnson J.R., Klumpp D.J., and Schaeffer A.J. Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli. Infect Immun 75 (2007) 5353-5360. Comparing clinical isolates with laboratory E. coli isolates, the authors show that UPEC isolates specifically suppress the innate immune response of uroepithelial cells including cytokine/chemokine secretion and neutrophil recruitment.
40. Hunstad D.A., Justice S.S., Hung C.S., Lauer S.R., and Hultgren S.J. Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli. Infect Immun 73 (2005) 3999-4006
41. Justice S.S., Hunstad D.A., Harper J.R., Duguay A.R., Pinkner J.S., Bann J., Frieden C., Silhavy T.J., and Hultgren S.J. Periplasmic peptidyl prolyl cis-trans isomerases are not essential for viability, but SurA is required for pilus biogenesis in Escherichia coli. J Bacteriol 187 (2005) 7680-7686
42. Fischer H., Yamamoto M., Akira S., Beutler B., and Svanborg C. Mechanism of pathogen-specific TLR4 activation in the mucosa: fimbriae, recognition receptors and adaptor protein selection. Eur J Immunol 36 (2006) 267-277
43. Godaly G., Otto G., Burdick M.D., Strieter R.M., and Svanborg C. Fimbrial lectins influence the chemokine repertoire in the urinary tract mucosa. Kidney Int 71 (2007) 778-786. The ability of fimbriae expressed on UPEC to differentially modulate the chemokine and cytokine responses mediated by TLR4 on uroepithelial cells is described.