Molecular Defense Mechanisms during Urinary Tract Infection

Se Young Choi; In Ho Chang

doi:10.14777/uti.2015.10.02.57

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Choi and Chang: Molecular Defense Mechanisms during Urinary Tract Infection

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Urogenit Tract Infect 2015;10(2):57-66.

Published online: 19 October 2015

DOI: https://doi.org/10.14777/uti.2015.10.02.57

Molecular Defense Mechanisms during Urinary Tract Infection

Se Young Choi, In Ho Chang

Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea

Correspondence to: In Ho Chang http://orcid.org/0000-0003-0240-1310 Department of Urology, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea Tel: +82-2-6299-1785, Fax: +82-2-6294-1406 E-mail: caucih@cau.ac.kr

Received 15 July 2015 Revised 28 July 2015 Accepted 28 July 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Urinary tract infections, Molecular biology

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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
TLR7	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.

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