Chapter 22 : Innate Immune Responses to Bladder Infection

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Innate Immune Responses to Bladder Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817404/9781555817398_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555817404/9781555817398_Chap22-2.gif


The urinary tract (UT) consists of the kidneys, ureters, bladder, and urethra, all of which with the exception of the lower urethra are presumed to be sterile. Because of its close proximity to the gut, the lower UT is constantly exposed to a barrage of gut bacteria. However, the bladder remains for the most part free of infection. The resistance of the bladder to active microbial colonization is due to both anatomical design as well as secreted antimicrobial compounds of the urothelium. The apical face of the urothelium is covered by uroplakin plaques and is coated by mucus, which discourages adherence and invasion of most microorganisms ( ). Because of its role in storing urine for extended periods of time, the urothelium of the bladder has an additional role in protecting the underlying tissue from urine and its many toxic constituents. Since the bladder and urinary system as a whole need to constantly maintain the integrity of the urothelium, immune responses in the UT are often tightly regulated to minimize the extent of damage by quelling inflammation in a timely manner.

Citation: Hayes B, Abraham S. 2017. Innate Immune Responses to Bladder Infection, p 555-564. In Mulvey M, Klumpp D, Stapleton A (ed), Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.UTI-0024-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Wu XR,, Kong XP,, Pellicer A,, Kreibich G,, Sun TT . 2009. Uroplakins in urothelial biology, function, and disease. Kidney Int 75 : 11531165. [PubMed] [PubMed]
2. Grist M,, Chakraborty J . 1994. Identification of a mucin layer in the urinary bladder. Urology 44 : 2633.[PubMed]
3. Ronald A . 2003. The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon 49 : 7182.
4. Rosen DA,, Hooton TM,, Stamm WE,, Humphrey PA,, Hultgren SJ . 2007. Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med 4 : e329. doi:10.1371/journal.pmed.0040329.
5. Foxman B . 2003. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon 49 : 5370.[PubMed]
6. Foxman B . 2010. The epidemiology of urinary tract infection. Nat Rev Urol 7 : 653660.[PubMed]
7. Nielubowicz GR,, Mobley HL . 2010. Host-pathogen interactions in urinary tract infection. Nat Rev Urol 7 : 430441.[PubMed]
8. Ratner JJ,, Thomas VL,, Sanford BA,, Forland M . 1981. Bacteria-specific antibody in the urine of patients with acute pyelonephritis and cystitis. J Infect Dis 143 : 404412.[PubMed]
9. Song J,, Duncan MJ,, Li G,, Chan C,, Grady R,, Stapleton A,, Abraham SN . 2007. A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells. PLoS Pathog 3 : e60. doi:10.1371/journal.ppat.0030060.
10. Nagamatsu K,, Hannan TJ,, Guest RL,, Kostakioti M,, Hadjifrangiskou M,, Binkley J,, Dodson K,, Raivio TL,, Hultgren SJ . 2015. Dysregulation of Escherichia coli α-hemolysin expression alters the course of acute and persistent urinary tract infection. Proc Natl Acad Sci USA 112 : E871E880.[PubMed]
11. Chromek M,, Slamová Z,, Bergman P,, Kovács L,, Podracká L,, Ehrén I,, Hökfelt 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 : 636641.[PubMed]
12. 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 : 16331642.[PubMed]
13. Danka ES,, Hunstad DA . 2015. Cathelicidin augments epithelial receptivity and pathogenesis in experimental Escherichia coli cystitis. J Infect Dis 211 : 11641173.[PubMed]
14. 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 : 615625.[PubMed]
15. Jaillon S,, Moalli F,, Ragnarsdottir B,, Bonavita E,, Puthia M,, Riva F,, Barbati E,, Nebuloni M,, Cvetko Krajinovic L,, Markotic A,, Valentino S,, Doni A,, Tartari S,, Graziani G,, Montanelli A,, Delneste Y,, Svanborg C,, Garlanda C,, Mantovani A . 2014. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40 : 621632.[PubMed]
16. Chen Y,, Guo X,, Deng FM,, Liang FX,, Sun W,, Ren M,, Izumi T,, Sabatini DD,, Sun TT,, Kreibich G . 2003. Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes. Proc Natl Acad Sci USA 100 : 1401214017.[PubMed]
17. Bishop BL,, Duncan MJ,, Song J,, Li G,, Zaas D,, Abraham SN . 2007. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med 13 : 625630.[PubMed]
18. Song J,, Bishop BL,, Li G,, Grady R,, Stapleton A,, Abraham SN . 2009. TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. Proc Natl Acad Sci USA 106 : 1496614971.[PubMed]
19. Miao Y,, Wu J,, Abraham SN . 2016. Ubiquitination of innate immune regulator TRAF3 orchestrates expulsion of intracellular bacteria by exocyst complex. Immunity 45 : 94105.[PubMed]
20. Miao Y,, Li G,, Zhang X,, Xu H,, Abraham SN . 2015. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell 161 : 13061319.[PubMed]
21. Elliott TSJ,, Reed L,, Slack RCB,, Bishop MC . 1985. Bacteriology and ultrastructure of the bladder in patients with urinary tract infections. J Infect 11 : 191199.[PubMed]
22. Cheng Y,, Chen Z,, Gawthorne JA,, Mukerjee C,, Varettas K,, Mansfield KJ,, Schembri MA,, Moore KH . 2016. Detection of intracellular bacteria in exfoliated urothelial cells from women with urge incontinence. Pathog Dis 74 : 74. [PubMed]
23. 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 : 14941497.[PubMed]
24. Mysorekar IU,, Isaacson-Schmid M,, Walker JN,, Mills JC,, Hultgren SJ . 2009. Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection. Cell Host Microbe 5 : 463475.[PubMed]
25. Shin K,, Lee J,, Guo N,, Kim J,, Lim A,, Qu L,, Mysorekar IU,, Beachy PA . 2011. Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472 : 110114.[PubMed]
26. Godaly G,, Bergsten G,, Hang L,, Fischer H,, Frendéus B,, Lundstedt AC,, Samuelsson M,, Samuelsson P,, Svanborg C . 2001. Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection. J Leukoc Biol 69 : 899906.[PubMed]
27. Schiwon M,, Weisheit C,, Franken L,, Gutweiler S,, Dixit A,, Meyer-Schwesinger C,, Pohl JM,, Maurice NJ,, Thiebes S,, Lorenz K,, Quast T,, Fuhrmann M,, Baumgarten G,, Lohse MJ,, Opdenakker G,, Bernhagen J,, Bucala R,, Panzer U,, Kolanus W,, Gröne HJ,, Garbi N,, Kastenmüller W,, Knolle PA,, Kurts C,, Engel DR . 2014. Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156 : 456468.[PubMed]
28. Shahin RD,, Engberg I,, Hagberg L,, Svanborg Edén C . 1987. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local Gram-negative infection. J Immunol 138 : 34753480.[PubMed]
29. Haraoka M,, Hang L,, Frendéus B,, Godaly G,, Burdick M,, Strieter R,, Svanborg C . 1999. Neutrophil recruitment and resistance to urinary tract infection. J Infect Dis 180 : 12201229.[PubMed]
30. Hannan TJ,, Roberts PL,, Riehl TE,, van der Post S,, Binkley JM,, Schwartz DJ,, Miyoshi H,, Mack M,, Schwendener RA,, Hooton TM,, Stappenbeck TS,, Hansson GC,, Stenson WF,, Colonna M,, Stapleton AE,, Hultgren SJ . 2014. Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis. EBioMedicine 1 : 4657. doi:10.1016/j.ebiom.2014.10.011.
31. Abraham SN,, St John AL . 2010. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10 : 440452.[PubMed]
32. Abraham S,, Shin J,, Malaviya R . 2001. Type 1 fimbriated Escherichia coli-mast cell interactions in cystitis. J Infect Dis 183(Suppl 1): S51S55.[PubMed]
33. Chan CY,, St John AL,, Abraham SN . 2013. Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38 : 349359.[PubMed]
34. Malaviya R,, Gao Z,, Thankavel K,, van der Merwe PA,, Abraham SN . 1999. The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. Proc Natl Acad Sci USA 96 : 81108115.[PubMed]
35. Soruri A,, Grigat J,, Forssmann U,, Riggert J,, Zwirner J . 2007. beta-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur J Immunol 37 : 24742486.[PubMed]
36. Säve S,, Persson K . 2010. Extracellular ATP and P2Y receptor activation induce a proinflammatory host response in the human urinary tract. Infect Immun 78 : 36093615.[PubMed]
37. Jang TY,, Kim YH . 2015. Interleukin-33 and mast cells bridge innate and adaptive immunity: from the allergologist’s perspective. Int Neurourol J 19 : 142150.[PubMed]
38. Mysorekar IU,, Hultgren SJ . 2006. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA 103 : 1417014175.[PubMed]
39. Mulvey MA,, Schilling JD,, Hultgren SJ . 2001. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun 69 : 45724579.[PubMed]
40. Michlewska S,, Dransfield I,, Megson IL,, Rossi AG . 2009. Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-alpha. FASEB J 23 : 844854.[PubMed]
41. Mora-Bau G,, Platt AM,, van Rooijen N,, Randolph GJ,, Albert ML,, Ingersoll MA . 2015. Macrophages subvert adaptive immunity to urinary tract infection. PLoS Pathog 11 : e1005044. doi:10.1371/journal.ppat.1005044. [PubMed]
42. Jones-Carson J,, Balish E,, Uehling DT . 1999. Susceptibility of immunodeficient gene-knockout mice to urinary tract infection. J Urol 161 : 338341.[PubMed]
43. Sivick KE,, Schaller MA,, Smith SN,, Mobley HL . 2010. The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection. J Immunol 184 : 20652075.[PubMed]
44. Engel D,, Dobrindt U,, Tittel A,, Peters P,, Maurer J,, Gütgemann 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 : 61006107.[PubMed]
45. Godaly G,, Ambite I,, Svanborg C . 2015. Innate immunity and genetic determinants of urinary tract infection susceptibility. Curr Opin Infect Dis 28 : 8896.[PubMed]
46. Lichodziejewska-Niemierko M,, Topley N,, Smith C,, Verrier-Jones K,, Williams JD . 1995. P1 blood group phenotype, secretor status in patients with urinary tract infections. Clin Nephrol 44 : 376379.[PubMed]
47. Ginaldi L,, Loreto MF,, Corsi MP,, Modesti M,, De Martinis M . 2001. Immunosenescence and infectious diseases. Microbes Infect 3 : 851857.[PubMed]
48. Ginaldi L,, De Martinis M,, D’Ostilio A,, Marini L,, Loreto MF,, Quaglino D . 1999. The immune system in the elderly. III. Innate immunity. Immunol Res 20 : 117126.
49. Hextall A,, Cardozo L . 2001. The role of estrogen supplementation in lower urinary tract dysfunction. Int Urogynecol J Pelvic Floor Dysfunct 12 : 258261.[PubMed]
50. Foxman B . 1999. Urinary tract infection in postmenopausal women. Curr Infect Dis Rep 1 : 367370.[PubMed]
51. Wang C,, Symington JW,, Ma E,, Cao B,, Mysorekar IU . 2013. Estrogenic modulation of uropathogenic Escherichia coli infection pathogenesis in a murine menopause model. Infect Immun 81 : 733739.[PubMed]
52. Klemm P,, Roos V,, Ulett GC,, Svanborg C,, Schembri MA . 2006. Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen. Infect Immun 74 : 781785.[PubMed]
53. Lutay N,, Ambite I,, Grönberg Hernandez J,, Rydström G,, Ragnarsdóttir B,, Puthia M,, Nadeem A,, Zhang J,, Storm P,, Dobrindt U,, Wullt B,, Svanborg C . 2013. Bacterial control of host gene expression through RNA polymerase II. J Clin Invest 123 : 23662379.[PubMed]
54. Ferrières L,, Hancock V,, Klemm P . 2007. Biofilm exclusion of uropathogenic bacteria by selected asymptomatic bacteriuria Escherichia coli strains. Microbiology 153 : 17111719.[PubMed]
55. Horwitz D,, McCue T,, Mapes AC,, Ajami NJ,, Petrosino JF,, Ramig RF,, Trautner BW . 2015. Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference. J Infect 71 : 358367.[PubMed]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error