Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

Abstract

The innate immune system responds in a rapid, initially nonspecific manner to infection in the urinary tract. There are many molecules and cells involved in this response. These include: antimicrobial peptides, toll-like receptors, chemokines, cytokines, and neutrophils. The most common cause of urinary tract infections (UTIs) are uropathogenic Escherichia coli (UPEC). The innate immune system responds to the presence of flagella, fimbriae, and the lipopolysaccharide outer membrane of these bacteria. Antimicrobial peptides are used to lyse the bacteria and also prevent the bacteria from binding to epithelial cells in the urinary tract. The toll-like receptors sense the presence of the bacteria and signal for the production of molecules that cause immune and inflammation responses. The various chemokines and cytokines such as CXCL8, CCL2, interleukins (IL-6, IL-8, IL-10, IL-17A), and granulocyte colony stimulating factor (G-CSF), are used for much of the signaling in innate immunity. In addition, neutrophils play a major role in rapid removal of invading bacteria. The rapid innate immune response is designed to remove most of the bacteria within 24 hours in an uncomplicated UTI. This review presents an overview of the innate immune response to UTIs caused by UPEC and the host molecules and cells involved.

Toll‐like receptors: The role in bladder cancer development, progression and immunotherapy

“…The target ligands of TLR4 are LPS, type I and P‐fimbriae, HSPs (60, 70, 90) which are important in eradication of Uropathogenic Escherichia coli (UPEC) from the bladder epithelial cells. The expression level of TLR4 molecules is depended on severity of UTIs …”

The role of toll-like receptors (TLRs) in urinary tract infections (UTIs)

“…In accordance with several studies, the urothelial cells act as sensitive biosensors which induce the proinflammatory cytokines and other immunologic responses in the presence of pathogens. Moreover, the microbial virulence factors and the quality of the host's immune responses directly determine the level of urinary tract infections (UTIs) severity from benign to deathful and acute to chronic [1–3]. …”

“…Immune cells are able to produce and secrete all members of PRR families such as NLRs, RLRs, CLRs, and TLRs. The PRRs like TLRs are important immunologic biosensors for tracing pathogens within the host's cells and tissues by recognition of microbial conserved components, termed pathogen association molecular patterns (PAMPs) [1, 4–6, 8]. …”

“…By the entrance of uropathogenic microorganisms into the urinary tract, the innate immune responses are going to be activated via expression of the related TLRs within the urothelial cells of bladder (cystitis) and kidneys (nephritis). Consequently, the expression of related TLRs triggers different cascading responses including the release of chemokines, interferons, interleukins, antimicrobial substances and proinflammatory cytokines [1, 6, 12, 14, 17, 19, 20, 22]. …”

“…For example, the level of secretion of TLR4 molecules in patients with reduced infection of asymptomatic bacteriuria is significantly less than patients with acute and symptomatic UTIs. A healthy immune system is able to clear the urinary tract from microbial pathogens such as UPEC from one up to a few days [1, 3, 4, 9, 11, 12, 14, 19, 20, 35]. The LPS molecules which are situated in the outer membrane of Gram –ive bacteria such as the Enterobacteriaceae family members, trigger the expression of TLR4 molecules.…”