1887

Chapter 21 : Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817213/9781555817084_Chap21-1.gif /docserver/preview/fulltext/10.1128/9781555817213/9781555817084_Chap21-2.gif

Abstract:

Microbial determinants of acute-disease severity and tissue damage have been extensively studied, but less is known about genetic variation influencing host susceptibility. This chapter discusses two candidate genes with strong effects on the innate immune response and the antibacterial defense in the urinary tract and with major but opposite effects on urinary tract infection (UTI) susceptibility. The chapter explains that defects in TLR4 expression are protective and associated with asymptomatic bacteriuria (ABU) while defects in CXCR1 expression promote acute pyelonephritis (APN) and renal scarring. C3H/HeJ mice, then known as lipopolysaccharide (LPS)-nonresponder mice, had an increased susceptibility to UTI, as shown by delayed bacterial clearance. It also had an impaired innate immune response, suggesting that defects in innate immunity are of great importance for the antibacterial defense of the urinary tract. Studies of the murine model showed that the antibacterial defense of the urinary tract mucosa relies on innate immunity and that TLR4 plays a central role in the early host defense against infection. The results suggest that genetic variation of the TLR4 promoter is an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility. It was found that the protein expression was reduced and additionally the level of CXCR1 transcript and protein expression was lower in this new subset of pediatric patients. There is a great clinical need to identify genetic variants that improve resistance or increase susceptibility to infectious pathogens.

Citation: Ragnarsdóttir B, Svanborg C. 2012. Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection, p 358-378. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch21

Key Concept Ranking

Mouse mammary tumor virus
0.46285892
Bacterial Vaccines
0.41584086
0.46285892
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

TLR4 is crucial for recognition of gram-negative bacteria and is best known as the LPS receptor. CD14 is a coreceptor for TLR4 and is essential for LPS recognition. Epithelial cells are, unlike macrophages and polymorphonuclear neutrophils, CD14 negative and as a result do not respond to LPS or commensal-like bacteria. However, epithelial cells respond in a pathogen-specific way and are activated by both P-and type 1-fimbriated but in different ways. P fimbriae bind to the Galα1-4Galb receptor epitope in the globoseries of glycosphingolipids (GSLs), resulting in ceramide release and activation of epithelial cells through a TLR4 and the TRIF/TRAM-dependent pathway. Type 1 fimbriae bind α-mannosylated glycoproteins (MGPs) and activate epithelial cells through TLR4 but through MyD88-dependent mechanisms. doi:10.1128/9781555817213.ch21f01

Citation: Ragnarsdóttir B, Svanborg C. 2012. Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection, p 358-378. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Three-generation pedigrees reveal a genetic predisposition to UTI. An accumulation of pyelonephritis was found in the relatives of the APN-prone patients (shown in red), while most of the UTI incidents in the control families were single episodes of cystitis (shown in gray), often associated with pregnancy. The arrows indicate the index APN-prone children. Partially reprinted from the ( ) with permission of the publisher. doi:10.1128/9781555817213.ch21f02

Citation: Ragnarsdóttir B, Svanborg C. 2012. Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection, p 358-378. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817213.chap21
1. Agace, W.,, S. Hedges,, U. Andersson,, J. Andersson,, M. Ceska,, and C. Svanborg. 1993a. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect. Immun. 61:602609.
2. Agace, W.,, S. Hedges,, M. Ceska,, and C. Svanborg. 1993b. IL-8 and the neutrophil response to mucosal Gram negative infection. J. Clin. Investig. 92:780785.
3. Ahuja, S. K.,, and P. M. Murphy 1996. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. J. Biol. Chem. 271:2054520550.
4. Allen, A.,, S. Obaro,, K. Bojang,, A. A. Awomoyi,, B. M. Greenwood,, H. Whittle,, G. Sirugo,, and M. J. Newport. 2003. Variation in Toll-like receptor 4 and susceptibility to group A meningococcal meningitis in Gambian children. Pediatr. Infect. Dis. J. 22:10181019.
5. Anderson, K. V.,, G. Jurgens,, and C. Nusslein-Volhard. 1985. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell 42:779789.
6. Arbour, N. C.,, E. Lorenz,, B. C. Schutte,, J. Zabner,, J. N. Kline,, M. Jones,, K. Frees,, J. L. Watt,, and D. A. Schwartz. 2000. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 25:187191.
7. Backhed, F.,, L. Meijer,, S. Normark,, and A. Richter-Dahlfors. 2002. TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14. Cell. Microbiol. 4:493501.
8. Baggiolini, M. 1998. Chemokines and leukocyte traffic. Nature 392:565568.
9. Bergsten, G.,, M. Samuelsson,, B. Wullt,, I. Leijonhufvud,, H. Fischer,, and C. Svanborg. 2004. PapG-dependent adherence breaks mucosal inertia and triggers the innate host response. J. Infect. Dis. 189:17341742.
10. Bergsten, G.,, B. Wullt,, and C. Svanborg. 2005. Escherichia coli, fimbriae, bacterial persistence and host response induction in the human urinary tract. Int. J. Med. Microbiol. 295:487502.
11. Bianchi, M. E. 2007. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81:15.
12. Bihl, F.,, L. Salez,, M. Beaubier,, D. Torres,, L. Lariviere,, L. Laroche,, A. Benedetto,, D. Martel,, J. M. Lapointe,, B. Ryffel,, and D. Malo. 2003. Overexpression of Toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in transgenic mice. J. Immunol. 170:61416150.
13. Bowie, A.,, E. Kiss-Toth,, J. A. Symons,, G. L. Smith,, S. K. Dower,, and L. A. O’Neill. 2000. A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc. Natl. Acad. Sci. USA 97:1016210167.
14. Breunis, W. B.,, M. H. Biezeveld,, J. Geissler,, I. M. Kuipers,, J. Lam,, J. Ottenkamp,, A. Hutchinson,, R. Welch,, S. J. Chanock,, and T. W. Kuijpers. 2007. Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease. Clin. Exp. Immunol. 150:8390.
15. Brikos, C.,, and L. A. O’Neill. 2008. Signalling of toll-like receptors. Handb. Exp. Pharmacol. 2008(183):2150.
16. Burns, K.,, S. Janssens,, B. Brissoni,, N. Olivos,, R. Beyaert, and J. Tschopp. 2003. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J. Exp. Med. 197:263268.
17. Burns, K.,, F. Martinon,, C. Esslinger,, H. Pahl,, P. Schneider,, J. L. Bodmer,, F. DiMarco,, L. French,, and J. Tschopp. 1998. MyD88, an adapter protein involved in interleukin-1 signaling. J. Biol. Chem. 273:1220312209.
18. Calvano, J. E.,, D. J. Bowers,, S. M. Coyle,, M. Macor,, M. T. Reddell,, A. Kumar,, S. E. Calvano,, and S. F. Lowry. 2006. Response to systemic endotoxemia among humans bearing polymorphisms of the Toll-like receptor 4 (hTLR4). Clin. Immunol. 121:186190.
19. Cao, Z.,, J. Xiong,, M. Takeuchi,, T. Kurama,, and D. V. Goeddel. 1996. TRAF6 is a signal transducer for interleukin-1. Nature 383:443446.
20. Carty, M.,, R. Goodbody,, M. Schroder,, J. Stack,, P. N. Moynagh,, and A. G. Bowie. 2006. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat. Immunol. 7:10741081.
21. Casanova, J. L.,, and L. Abel. 2007. Primary immunodeficiencies: a field in its infancy. Science 317:617619.
22. Cheong, J. Y.,, S. W. Cho,, J. Y. Choi,, J. A. Lee,, M. H. Kim,, J. E. Lee,, K. B. Hahm,, and J. H. Kim. 2007. RANTES, MCP-1, CCR2, CCR5, CXCR1 and CXCR4 gene polymorphisms are not associated with the outcome of hepatitis B virus infection: results from a large scale single ethnic population. J. Korean Med. Sci. 22:529535.
23. Chotivanich, K.,, R. Udomsangpetch,, K. Pattanapanyasat,, W. Chierakul,, J. Simpson,, S. Looareesuwan,, and N. White. 2002. Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. Blood 100:11721176.
24. Chuntharapai, A.,, and K. J. Kim. 1995. Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor. J. Immunol. 155:25872594.
25. Cirl, C.,, A. Wieser,, M. Yadav,, S. Duerr,, S. Schubert,, H. Fischer,, D. Stappert,, N., Wantia,, N. Rodriguez,, H. Wagner,, C. Svanborg,, and T. Miethke. 2008. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-receptor domain-containing proteins. Nat. Med. 14:399406.
26. Copeman, J. B.,, F. Cucca,, C. M. Hearne,, R. J. Cornall,, P. W. Reed,, K. S. Ronningen,, D. E. Undlien,, L. Nistico,, R. Buzzetti,, R. Tosi, et al. 1995. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33. Nat. Genet. 9:8085.
27. Cornelis, F.,, S. Faure,, M. Martinez,, J. F. Prud’homme,, P. Fritz,, C. Dib,, H. Alves,, P. Barrera,, N. de Vries,, A. Balsa,, D. Pascual-Salcedo,, K. Maenaut,, R. Westhovens,, P. Migliorini,, T. H. Tran,, A. Delaye,, N. Prince,, C. Lefevre,, G. Thomas,, M. Poirier,, S. Soubigou,, O. Alibert,, S. Lasbleiz,, S. Fouix,, C. Bouchier,, F. Liote,, M. N. Loste,, V. Lepage,, D. Charron,, G. Gyapay,, A. Lopes-Vaz,, D. Kuntz,, T. Bardin,, and J. Weissenbach. 1998. New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. Proc. Natl. Acad. Sci. USA 95:1074610750.
28. Deng, L.,, C. Wang,, E. Spencer,, L. Yang,, A. Braun,, J. You,, C. Slaughter,, C. Pickart,, and Z. J. Chen. 2000. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103:351361.
29. Doffinger, R.,, A. Smahi,, C. Bessia,, F. Geissmann,, J. Feinberg,, A. Durandy,, C. Bodemer,, S. Kenwrick,, S. Dupuis-Girod,, S. Blanche,, P. Wood,, S. H. Rabia,, D. J. Headon,, P. A. Overbeek,, F. Le Deist,, S. M. Holland,, K. Belani,, D. S. Kumararatne,, A. Fischer,, R. Shapiro,, M. E. Conley,, E. Reimund,, H. Kalhoff,, M. Abinun,, A. Munnich,, A. Israel,, G. Courtois,, and J. L. Casanova. 2001. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat. Genet. 27:277285.
30. Dunne, A.,, M. Ejdeback,, P. L. Ludidi,, L. A. O’Neill,, and N. J. Gay. 2003. Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. J. Biol. Chem. 278:4144341451.
31. Edfeldt, K.,, A. M. Bennet,, P. Eriksson,, J. Frostegard,, B. Wiman,, A. Hamsten,, G. K. Hansson,, U. de Faire,, and Z. Q. Yan. 2004. Association of hypo-responsive toll-like receptor 4 variants with risk of myocardial infarction. Eur. Heart J. 25:14471453.
32. Fearns, C.,, Q. Pan,, J. C. Mathison,, and T. H. Chuang. 2006. Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following disruption of Hsp90 binding. J. Biol. Chem. 281:3459234600.
33. Ferwerda, B.,, M. B. McCall,, S. Alonso,, E. J. Giamarellos-Bourboulis,, M. Mouktaroudi,, N. Izagirre,, D. Syafruddin,, G. Kibiki,, T. Cristea,, A. Hijmans,, L. Hamann,, S. Israel,, G. ElGhazali,, M. Troye-Blomberg,, O. Kumpf,, B. Maiga,, A. Dolo,, O. Doumbo,, C. C. Hermsen,, A. F. Stalenhoef,, R. van Crevel,, H. G. Brunner,, D. Y. Oh,, R. R. Schumann,, C. de la Rua,, R. Sauerwein,, B. J. Kullberg,, A. J. van der Ven,, J. W. van der Meer,, and M. G. Netea. 2007. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc. Natl. Acad. Sci. USA 104:1664516650.
34. Fijen, C. A.,, E. J. Kuijper,, A. J. Hannema,, A. G. Sjoholm,, and J. P. van Putten. 1989. Complement deficiencies in patients over ten years old with meningococcal disease due to uncommon serogroups. Lancet ii:585588.
35. Fischer, H.,, P. Ellstrom,, K. Ekstrom,, L. Gustafsson,, M. Gustafsson,, and C. Svanborg. 2007. Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4. Cell. Microbiol. 9:12391251.
36. Fitzgerald, K. A.,, E. M. Palsson-McDermott,, A. G. Bowie,, C. A. Jefferies,, A. S. Mansell,, G. Brady,, E. Brint,, A. Dunne,, P. Gray,, M. T. Harte,, D. McMurray,, D. E. Smith,, J. E. Sims,, T. A. Bird,, and L. A. O’Neill. 2001. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413:7883.
37. Fitzgerald, K. A.,, D. C. Rowe,, B. J. Barnes,, D. R. Caffrey,, A. Visintin,, E. Latz,, B. Monks,, P. M. Pitha,, and D. T. Golenbock. 2003. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J. Exp. Med. 198:10431055.
38. Frendeus, B.,, G. Godaly,, L. Hang,, D. Karpman,, A. C. Lundstedt,, and C. Svanborg. 2000. Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J. Exp. Med. 192:881890.
39. Frendeus, B.,, G. Godaly,, L. Hang,, D. Karpman,, and C. Svanborg. 2001a. Interleukin-8 receptor deficiency confers susceptibility to acute pyelonephritis. J. Infect. Dis. 183(Suppl. 1):S56S60.
40. Frendeus, B.,, C. Wachtler,, M. Hedlund,, H. Fischer,, P. Samuelsson,, M. Svensson,, and C. Svanborg. 2001b. Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. Mol. Microbiol. 40:3751.
41. Fu, W.,, Y. Zhang,, J. Zhang,, and W. F. Chen. 2005. Cloning and characterization of mouse homolog of the CXC chemokine receptor CXCR1. Cytokine 31:917.
42. Gaffney, P. M.,, G. M. Kearns,, K. B. Shark,, W. A. Ortmann,, S. A. Selby,, M. L. Malmgren,, K. E. Rohlf,, T. C. Ockenden,, R. P. Messner,, R. A. King,, S. S. Rich,, and T. W. Behrens. 1998. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. Proc. Natl. Acad. Sci. USA 95:1487514879.
43. Gay, N. J.,, and M. Gangloff. 2008. Structure of toll-like receptors. Handb. Exp. Pharmacol. 2008(183):181200.
44. Godaly, G.,, G. Bergsten,, L. Hang,, H. Fischer,, B. Frendeus,, A. C. Lundstedt,, M. Samuelsson,, P. Samuelsson,, and C. Svanborg. 2001. Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection. J. Leukoc. Biol. 69:899906.
45. Godaly, G.,, L. Hang,, B. Frendeus,, and C. Svanborg. 2000. Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J. Immunol. 165: 52875294.
46. Godaly, G.,, A. E. Proudfoot,, R. E. Offord,, C. Svanborg,, and W. W. Agace. 1997. Role of epithelial interleukin-8 (IL-8) and neutrophil IL-receptor A in Escherichia coli-induced transuroepithelial neutrophil migration. Infect. Immun. 65:34513456.
47. Gray, P.,, A. Dunne,, C. Brikos,, C. A. Jefferies,, S. L. Doyle,, and L. A. O’Neill. 2006. MyD88 adapter-like (Mal) is phosphorylated by Bruton’s tyrosine kinase during TLR2 and TLR4 signal transduction. J. Biol. Chem. 281:1048910495.
48. Hacker, J.,, and J. B. Kaper. 2000. Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54:641679.
49. Hagberg, L.,, D. Briles,, and C. Svanborg-Edén. 1985. Evidence for separate genetic defects in C3H/HeJ and C3HeB/FeJ mice that affect the susceptibility to Gram-negative infections. J. Immunol. 134:41184122.
50. Hang, L.,, B. Frendeus,, G. Godaly,, and C. Svanborg. 2000. Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis. J. Infect. Dis. 182:17381748.
51. Hanson, L. A.,, S. Ahlstedt,, A. Fasth,, U. Jodal,, B. Kaijser,, P. Larsson,, U. Lindberg,, S. Olling,, A. Sohl-Akerlund,, and C. Svanborg-Eden. 1977. Antigens of Escherichia coli, human immune response, and the pathogenesis of urinary tract infections. J. Infect. Dis. 136(Suppl.):S144S149.
52. Haraoka, M.,, L. Hang,, B. Frendeus,, G. Godaly,, M. Burdick,, R. Strieter,, and C. Svanborg. 1999. Neutrophil recruitment and resistance to urinary tract infection. J. Infect. Dis. 180:12201229.
53. Hawn, T. R.,, D. Scholes,, S. S. Li,, H. Wang,, Y. Yang,, P. L. Roberts,, A. E. Stapleton,, M. Janer,, A. Aderem,, W. E. Stamm,, L. P. Zhao,, and T. M. Hooton. 2009a. Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLoS One 4:e5990.
54. Hawn, T. R.,, D. Scholes,, H. Wang,, S. S. Li,, A. E. Stapleton,, M. Janer,, A. Aderem,, W. E. Stamm,, L. P. Zhao,, and T. M. Hooton. 2009b. Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women. PLoS One 4:e8300.
55. Hawn, T. R.,, A. Verbon,, K. D. Lettinga,, L. P. Zhao,, S. S. Li,, R. J. Laws,, S. J. Skerrett,, B. Beutler,, L. Schroeder,, A. Nachman,, A. Ozinsky,, K. D. Smith,, and A. Aderem. 2003. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J. Exp. Med. 198:15631572.
56. Hedlund, M.,, B. Frendeus,, C. Wachtler,, L. Hang,, H. Fischer,, and C. Svanborg. 2001. Type 1 fimbriae deliver an LPS-and TLR4-dependent activation signal to CD14-negative cells. Mol. Microbiol. 39:542552.
57. Hedlund, M.,, Å. Nilsson,, R. D. Duan,, and C. Svanborg. 1998. Sphingomyelin, glycosphingolipids and ceramide signalling in cells exposed to P fimbriated Escherichia coli. Mol. Microbiol. 29:12971306.
58. Hedlund, M.,, M. Svensson,, A. Nilsson,, R. D. Duan,, and C. Svanborg. 1996. Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli. J. Exp. Med. 183: 10371044.
59. Hedlund, M.,, C. Wachtler,, E. Johansson,, L. Hang,, J. E. Somerville,, R. P. Darveau,, and C. Svanborg. 1999. P fimbriae-dependent, lipopolysaccharide-independent activation of epithelial cytokine responses. Mol. Microbiol. 33:693703.
60. Hoebe, K.,, X. Du,, P. Georgel,, E. Janssen,, K. Tabeta,, S. O. Kim,, J. Goode,, P. Lin,, N. Mann,, S. Mudd,, K. Crozat,, S. Sovath,, J. Han,, and B. Beutler. 2003. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743748.
61. Holmes, W. E.,, J. Lee,, W. J. Kuang,, G. C. Rice,, and W. I. Wood. 1991. Structure and functional expression of a human interleukin-receptor. Science 253:12781280.
62. Hopkins, W. J.,, J. Elkahwaji,, L. M. Beierle,, G. E. Leverson,, and D. T. Uehling. 2007. Vaginal mucosal vaccine for recurrent urinary tract infections in women: results of a phase 2 clinical trial. J. Urol. 177:13491353; quiz 1591.
63. Hopkins, W. J.,, A. Gendron-Fitzpatrick,, E. Balish,, and D. T. Uehling. 1998. Time course and host responses to Escherichia coli urinary tract infection in genetically distinct mouse strains. Infect. Immun. 66:27982802.
64. Hopkins, W. J.,, D. T. Uehling,, and D. S. Wargowski. 1999. Evaluation of a familial predisposition to recurrent urinary tract infections in women. Am. J. Med. Genet. 83:422424.
65. Horng, T.,, G. M. Barton,, and R. Medzhitov. 2001. TIRAP: an adapter molecule in the Toll signaling pathway. Nat. Immunol. 2:835841.
66. Janssens, S.,, K. Burns,, E. Vercammen,, J. Tschopp,, and R. Beyaert. 2003. MyD88S, a splice variant of MyD88, differentially modulates NF-κB-and AP-1-dependent gene expression. FEBS Lett. 548:103107.
67. Kagan, J. C.,, and R. Medzhitov. 2006. Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125:943955.
68. Kaijser, B.,, S. Ahlstedt,, U. Jodal,, and S. Mårild. 1978. Possible clinical significance of O and K antibodies against infecting Escherichia coli in antimicrobial treatment of acute childhood pyelonephritis. Infection 6:S125S128.
69. Kaijser, B.,, L. A. Hanson,, U. Jodal,, G. Lidin-Janson,, and J. B. Robbins. 1977. Frequency of E. coli K antigens in urinary-tract infections in children. Lancet i:663666.
70. Kaijser, B.,, P. Larsson,, S. Olling,, and R. Schneerson. 1983. Protection against acute, ascending pyelonephritis caused by Escherichia coli in rats, using isolated capsular antigen conjugated to bovine serum albumin. Infect. Immun. 39:142146.
71. Kalis, C.,, B. Kanzler,, A. Lembo,, A. Poltorak,, C. Galanos,, and M. A. Freudenberg. 2003. Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice. Eur. J. Immunol. 33:798805.
72. Karin, M.,, and Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18:621663.
73. Karoly, E.,, A. Fekete,, N. F. Banki,, B. Szebeni,, A. Vannay,, A. J. Szabo,, T. Tulassay,, and G. S. Reusz. 2007. Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatr. Res. 61:371374.
74. Kato, H.,, N. Tsuchiya,, and K. Tokunaga. 2000. Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3. Genes Immun. 1:330337.
75. Kawai, T.,, O. Adachi,, T. Ogawa,, K. Takeda,, and S. Akira. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11:115122.
76. Kawai, T.,, and S. Akira. 2009. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21:317337.
77. Kawai, T.,, S. Sato,, K. J. Ishii,, C. Coban,, H. Hemmi,, M. Yamamoto,, K. Terai,, M. Matsuda,, J. Inoue,, S. Uematsu,, O. Takeuchi,, and S. Akira. 2004. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol. 5:10611068.
78. Kim, H. M.,, B. S. Park,, J. I. Kim,, S. E. Kim,, J. Lee,, S. C. Oh,, P. Enkhbayar,, N. Matsushima,, H. Lee,, O. J. Yoo,, and J. O. Lee. 2007. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130:906917.
79. Ko, Y. C.,, N. Mukaida,, S. Ishiyama,, A. Tokue,, T. Kawai,, K. Matsushima,, and T. Kasahara. 1993. Elevated interleukin-8 levels in the urine of patients with urinary tract infections. Infect. Immun. 61:13071314.
80. Kobayashi, K.,, L. D. Hernandez,, J. E. Galan,, C. A. Janeway, Jr.,, R. Medzhitov,, and R. A. Flavell. 2002. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191202.
81. Langermann, S.,, R. Mollby,, J. E. Burlein,, S. R. Palaszynski,, C. G. Auguste,, A. DeFusco,, R. Strouse,, M. A. Schenerman,, S. J. Hultgren,, J. S. Pinkner,, J. Winberg,, L. Guldevall,, M. Soderhall,, K. Ishikawa,, S. Normark,, and S. Koenig. 2000. Vaccination with FimH adhesin protects cynomolgus monkeys from colonization and infection by uropathogenic Escherichia coli. J. Infect. Dis. 181:774778.
82. Langermann, S.,, S. Palaszynski,, M. Barnhart,, G. Auguste,, J. S. Pinkner,, J. Burlein,, P. Barren,, S. Koenig,, S. Leath,, C. H. Jones,, and S. J. Hultgren. 1997. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science 276:607611.
83. Lichtinger, M.,, R. Ingram,, M. Hornef,, C. Bonifer,, and M. Rehli. 2007. Transcription factor PU.1 controls transcription start site positioning and alternative TLR4 promoter usage. J. Biol. Chem. 282:2687426883.
84. Lien, E.,, T. J. Sellati,, A. Yoshimura,, T. H. Flo,, G. Rawadi,, R. W. Finberg,, J. D. Carroll,, T. Espevik,, R. R. Ingalls,, J. D. Radolf,, and D. T. Golenbock. 1999. Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J. Biol. Chem. 274:3341933425.
85. Lomberg, H.,, L. A. Hanson,, B. Jacobsson,, U. Jodal,, H. Leffler,, and C. S. Eden. 1983. Correlation of P blood group, vesicoureteral reflux, and bacterial attachment in patients with recurrent pyelonephritis. N. Engl. J. Med. 308:11891192.
86. Lomberg, H.,, U. Jodal,, C. Svanborg-Edén,, H. Leffler,, and B. Samuelsson. 1981. P1 blood group and urinary tract infection. Lancet i:551552.
87. Lundstedt, A. C.,, I. Leijonhufvud,, B. Ragnarsdottir,, D. Karpman,, B. Andersson,, and C. Svanborg. 2007a. Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. J. Infect. Dis. 195:12271234.
88. Lundstedt, A. C.,, S. McCarthy,, M. C. Gustafsson,, G. Godaly,, U. Jodal,, D. Karpman,, I. Leijonhufvud,, C. Linden,, J. Martinell,, B. Ragnarsdottir,, M. Samuelsson,, L. Truedsson,, B. Andersson,, and C. Svanborg. 2007b. A genetic basis of susceptibility to acute pyelonephritis. PLoS One 2:e825.
89. Marsik, C.,, B. Jilma,, C. Joukhadar,, C. Mannhalter,, O. Wagner,, and G. Endler. 2005. The Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms influence the late inflammatory response in human endotoxemia. Clin. Chem. 51:21782180.
90. Matsushima, N.,, T. Tanaka,, P. Enkhbayar,, T. Mikami,, M. Taga,, K. Yamada,, and Y. Kuroki. 2007. Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics 8:124.
91. McGettrick, A. F.,, E. K. Brint,, E. M. Palsson-McDermott,, D. C. Rowe,, D. T. Golenbock,, N. J. Gay,, K. A. Fitzgerald,, and L. A. O’Neill. 2006. Trif-related adapter molecule is phosphorylated by PKCε during Toll-like receptor 4 signaling. Proc. Natl. Acad. Sci. USA 103:91969201.
92. Mockenhaupt, F. P.,, J. P. Cramer,, L. Hamann,, M. S. Stegemann,, J. Eckert,, N. R. Oh,, R. N. Otchwemah,, E. Dietz,, S. Ehrhardt,, N. W. Schroder,, U. Bienzle,, and R. R. Schumann. 2006. Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc. Natl. Acad. Sci. USA 103: 177182.
93. Moepps, B.,, E. Nuesseler,, M. Braun,, and P. Gierschik. 2006. A homolog of the human chemokine receptor CXCR1 is expressed in the mouse. Mol. Immunol. 43:897914.
94. Mogensen, T. H. 2009. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 22:240273.
95. Morgan, B. P.,, and A. Orren. 1998. Vaccination against meningococcus in complement-deficient individuals. Clin. Exp. Immunol. 114:327329.
96. Murphy, P. M.,, and H. L. Tiffany. 1991. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 253:12801283.
97. Oganesyan, G.,, S. K. Saha,, B. Guo,, J. Q. He,, A. Shahangian,, B. Zarnegar,, A. Perry,, and G. Cheng. 2006. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439:208211.
98. Olson, T. S.,, and K. Ley. 2002. Chemokines and chemokine receptors in leukocyte trafficking. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283:R7R28.
99. Ozinsky, A.,, K. D. Smith,, D. Hume,, and D. M. Underhill. 2000. Co-operative induction of pro-inflammatory signaling by Toll-like receptors. J. Endotoxin Res. 6:393396.
100. Palsson-McDermott, E. M.,, S. L. Doyle,, A. F. McGettrick,, M. Hardy,, H. Husebye,, K. Banahan,, M. Gong,, D. Golenbock,, T. Espevik,, and L. A. O’Neill. 2009. TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway. Nat. Immunol. 10:579586.
101. Pecha, B.,, D. Low,, and P. O’Hanley. 1989. Gal-Gal pili vaccines prevent pyelonephritis by piliated Escherichia coli in a murine model. Single-component Gal-Gal pili vaccines prevent pyelonephritis by homologous and heterologous piliated E. coli strains. J. Clin. Investig. 83:21022108.
102. Picard, C.,, A. Puel,, M. Bonnet,, C. L. Ku,, J. Bustamante,, K. Yang,, C. Soudais,, S. Dupuis,, J. Feinberg,, C. Fieschi,, C. Elbim,, R. Hitchcock,, D. Lammas,, G. Davies,, A. Al-Ghonaium,, H. Al-Rayes,, S. Al-Jumaah,, S. Al-Hajjar,, I. Z. Al-Mohsen,, H. H. Frayha,, R. Rucker,, T. R. Hawn,, A. Aderem,, H. Tufenkeji,, S. Haraguchi,, N. K. Day,, R. A. Good,, M. A. Gougerot-Pocidalo,, A. Ozinsky,, and J. L. Casanova. 2003. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299:20762079.
103. Poltorak, A.,, X. He,, I. Smirnova,, M. Y. Liu,, C. Van Huffel,, X. Du,, D. Birdwell,, E. Alejos,, M. Silva,, C. Galanos,, M. Freudenberg,, P. Ricciardi-Castagnoli,, B. Layton,, and B. Beutler. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:20852088.
104. Pugin, J.,, M. Schürer,, D. Leturcq,, A. Moriarty,, R. J. Ulevitch,, and P. S. Tobias. 1993. Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc. Natl. Acad. Sci. USA 90:27442748.
105. Ragnarsdottir, B.,, M. Samuelsson,, M. C. Gustafsson,, I. Leijonhufvud,, D. Karpman,, and C. Svanborg. 2007. Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J. Infect. Dis. 196:475484.
106. Rallabhandi, P.,, J. Bell,, M. S. Boukhvalova,, A. Medvedev,, E. Lorenz,, M. Arditi,, V. G. Hemming,, J. C. Blanco,, D. M. Segal,, and S. N. Vogel. 2006. Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling. J. Immunol. 177:322332.
107. Read, R. C.,, J. Pullin,, S. Gregory,, R. Borrow,, E. B. Kaczmarski,, F. S. di Giovine,, S. K. Dower,, C. Cannings,, and A. G. Wilson. 2001. A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J. Infect. Dis. 184:640642.
108. Rehli, M.,, A. Poltorak,, L. Schwarzfischer,, S. W. Krause,, R. Andreesen,, and B. Beutler. 2000. PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene. J. Biol. Chem. 275:97739781.
109. Roger, T.,, J. David,, M. P. Glauser,, and T. Calandra. 2001. MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 414: 920924.
110. Roger, T.,, I. Miconnet,, A. L. Schiesser,, H. Kai,, K. Miyake,, and T. Calandra. 2005. Critical role for Ets, AP-1 and GATA-like transcription factors in regulating mouse Toll-like receptor 4 (Tlr4) gene expression. Biochem. J. 387:355365.
111. Rowe, D. C.,, A. F. McGettrick,, E. Latz,, B. G. Monks,, N. J. Gay,, M. Yamamoto,, S. Akira,, L. A. O’Neill,, K. A. Fitzgerald,, and D. T. Golenbock. 2006. The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction. Proc. Natl. Acad. Sci. USA 103:62996304.
112. Rowe, J. A.,, D. H. Opi,, and T. N. Williams. 2009. Blood groups and malaria: fresh insights into pathogenesis and identification of targets for intervention. Curr. Opin. Hematol. 16:480487.
113. Roy, M. F.,, L. Lariviere,, R. Wilkinson,, M. Tam,, M. M. Stevenson,, and D. Malo. 2006. Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes. Genes Immun. 7:372383.
114. Samuelsson, P.,, L. Hang,, B. Wullt,, H. Irjala,, and C. Svanborg. 2004. Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect. Immun. 72:31793186.
115. Sato, S.,, M. Sugiyama,, M. Yamamoto,, Y. Watanabe,, T. Kawai,, K. Takeda,, and S. Akira. 2003. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J. Immunol. 171:43044310.
116. Schenck, M.,, A. Carpinteiro,, H. Grassme,, F. Lang,, and E. Gulbins. 2007. Ceramide: physiological and pathophysiological aspects. Arch. Biochem. Biophys. 462:171175.
117. Schilling, J. D.,, S. M. Martin,, C. S. Hung,, R. G. Lorenz,, and S. J. Hultgren. 2003. Toll-like receptor 4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 100:42034208.
118. Shahin, R.,, I. Engberg,, L. Hagberg,, and C. Svanborg-Edén. 1987. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J. Immunol. 10:34753480.
119. Sheedy, F. J.,, and L. A. O’Neill. 2007. The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. J. Leukoc. Biol. 82:196203.
120. Shimazu, R.,, S. Akashi,, H. Ogata,, Y. Nagai,, K. Fukudome,, K. Miyake,, and M. Kimoto. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189:17771782.
121. Silverblatt, F.,, and L. Cohen. 1979. Anti pili antibody affords protection against experimental ascending pyelonephritis. J. Clin. Investig. 64: 333336.
122. Sjoholm, A. G.,, G. Jonsson,, J. H. Braconier,, G. Sturfelt,, and L. Truedsson. 2006. Complement deficiency and disease: an update. Mol. Immunol. 43:7885.
123. Smith, R. J.,, L. M. Sam,, K. L. Leach,, and J. M. Justen. 1992. Postreceptor events associated with human neutrophil activation by interleukin-8. J. Leukoc. Biol. 52:1726.
124. Smithson, A.,, M. R. Sarrias,, J. Barcelo,, B. Suarez,, J. P. Horcajada,, S. M. Soto,, A. Soriano,, J. Vila,, J. A. Martinez,, J. Vives,, J. Mensa,, and F. Lozano. 2005. Expression of interleukin-8 receptors (CXCR1 and CXCR2) in premenopausal women with recurrent urinary tract infections. Clin. Diagn. Lab. Immunol. 12:13581363.
125. Sprenger, H.,, A. R. Lloyd,, R. G. Meyer,, J. A. Johnston,, and D. J. Kelvin. 1994. Genomic structure, characterization, and identification of the promoter of the human IL-8 receptor A gene. J. Immunol. 153:25242532.
126. Stapleton, A.,, E. Nudelman,, H. Clausen,, S. Hakomori,, and W. E. Stamm. 1992. Binding of uropathogenic Escherichia coli R45 to glycolipids extracted from vaginal epithelial cells is dependent on histo-blood group secretor status. J. Clin. Investig. 90:965972.
127. Svanborg, C.,, G. Bergsten,, H. Fischer,, G. Godaly,, M. Gustafsson,, D. Karpman,, A. C. Lundstedt,, B. Ragnarsdottir,, M. Svensson,, and B. Wullt. 2006. Uropathogenic Escherichia coli as a model of host-parasite interaction. Curr. Opin. Microbiol. 9:3339.
128. Svanborg Eden, C.,, D. Briles,, L. Hagberg,, J. McGhee,, and S. Michalec. 1985. Genetic factors in host resistance to urinary tract infection. Infection 13(Suppl. 2):S171S176.
129. Svensson, M.,, H. Irjala,, P. Alm,, B. Holmqvist,, A.-C. Lundstedt,, and C. Svanborg. 2005. Natural history of renal scarring in susceptible mIL-8Rh−/− mice. Kidney Int. 67:103110.
130. Tal, G.,, A. Mandelberg,, I. Dalal,, K. Cesar,, E. Somekh,, A. Tal,, A. Oron,, S. Itskovich,, A. Ballin,, S. Houri,, A. Beigelman,, O. Lider,, G. Rechavi,, and N. Amariglio. 2004. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J. Infect. Dis. 189:20572063.
131. Thomassen, E.,, B. R. Renshaw,, and J. E. Sims. 1999. Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 11:389399.
132. Thumbikat, P.,, C. Waltenbaugh,, A. J. Schaeffer,, and D. J. Klumpp. 2006. Antigen-specific responses accelerate bacterial clearance in the bladder. J. Immunol. 176:30803086.
133. Uehling, D. T.,, W. J. Hopkins,, E. Balish,, Y. Xing,, and D. M. Heisey. 1997. Vaginal mucosal immunization for recurrent urinary tract infection: phase II clinical trial. J. Urol. 157:20492052.
134. Uehling, D. T.,, W. J. Hopkins,, L. M. Beierle,, J. V. Kryger,, and D. M. Heisey. 2001. Vaginal mucosal immunization for recurrent urinary tract infection: extended phase II clinical trial. J. Infect. Dis. 183(Suppl. 1):S81S83.
135. Uehling, D. T.,, W. J. Hopkins,, L. A. Dahmer,, and E. Balish. 1994. Phase I clinical trial of vaginal mucosal immunization for recurrent urinary tract infection. J. Urol. 152:23082311.
136. Uehling, D. T.,, W. J. Hopkins,, J. E. Elkahwaji,, D. M. Schmidt,, and G. E. Leverson. 2003. Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. J. Urol. 170:867869.
137. Underhill, D. M.,, A. Ozinsky,, A. M. Hajjar,, A. Stevens,, C. B. Wilson,, M. Bassetti,, and A. Aderem. 1999. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811815.
138. Vasilescu, A.,, Y. Terashima,, M. Enomoto,, S. Heath,, V. Poonpiriya,, H. Gatanaga,, H. Do,, G. Diop,, T. Hirtzig,, P. Auewarakul,, D. Lauhakirti,, T. Sura,, P. Charneau,, S. Marullo,, A. Therwath,, S. Oka,, S. Kanegasaki,, M. Lathrop,, K. Matsushima,, J. F. Zagury,, and F. Matsuda. 2007. A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1 patients. Proc. Natl. Acad. Sci. USA 104:33543359.
139. von Bernuth, H.,, C. Picard,, Z. Jin,, R. Pankla,, H. Xiao,, C. L. Ku,, M. Chrabieh,, I. B. Mustapha,, P. Ghandil,, Y. Camcioglu,, J. Vasconcelos,, N. Sirvent,, M. Guedes,, A. B. Vitor,, M. J. Herrero-Mata,, J. I. Arostegui,, C. Rodrigo,, L. Alsina,, E. Ruiz-Ortiz,, M. Juan,, C. Fortuny,, J. Yague,, J. Anton,, M. Pascal,, H. H. Chang,, L. Janniere,, Y. Rose,, B. Z. Garty,, H. Chapel,, A. Issekutz,, L. Marodi,, C. Rodriguez-Gallego,, J. Banchereau,, L. Abel,, X. Li,, D. Chaussabel,, A. Puel,, and J. L. Casanova. 2008. Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321:691696.
140. Wald, D.,, J. Qin,, Z. Zhao,, Y. Qian,, M. Naramura,, L. Tian,, J. Towne,, J. E. Sims,, G. R. Stark,, and X. Li. 2003. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 4:920927.
141. Wang, C.,, L. Deng,, M. Hong,, G. R. Akkaraju,, J. Inoue,, and Z. J. Chen. 2001. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346351.
142. Wiles, T. J.,, R. R. Kulesus,, and M. A. Mulvey. 2008. Origins and virulence mechanisms of uropathogenic Escherichia coli. Exp. Mol. Pathol. 85:1119.
143. Wilkinson, N. C.,, and J. Navarro. 1999. PU.1 regulates the CXCR1 promoter. J. Biol. Chem. 274:438443.
144. Yadav, M.,, J. Zhang,, H. Fischer,, W. Huang,, N. Lutay,, C. Cirl,, J. Lum,, T. Miethke,, and C. Svanborg. 2010. Inhibition of TIR domain signaling by TcpC: MyD88-dependent and independent effects on Escherichia coli virulence. PLoS Pathog. 6:e1001120.
145. Yamamoto, M.,, S. Sato,, H. Hemmi,, K. Hoshino,, T. Kaisho,, H. Sanjo,, O. Takeuchi,, M. Sugiyama,, M. Okabe,, K. Takeda,, and S. Akira. 2003. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640643.
146. Yamamoto, M.,, S. Sato,, H. Hemmi,, S. Uematsu,, K. Hoshino,, T. Kaisho,, O. Takeuchi,, K. Takeda,, and S. Akira. 2003. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol. 4:11441150.
147. Yamamoto, M.,, S. Sato,, K. Mori,, K. Hoshino,, O. Takeuchi,, K. Takeda,, and S. Akira. 2002. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J. Immunol. 169:66686672.
148. Zhang, D.,, G. Zhang,, M. S. Hayden,, M. B. Greenblatt,, C. Bussey,, R. A. Flavell,, and S. Ghosh. 2004. A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303:15221526.

Tables

Generic image for table
TABLE 1

Some of the known TLR ligands (PAMPs)

Citation: Ragnarsdóttir B, Svanborg C. 2012. Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection, p 358-378. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch21

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