Disease relevance of Tlr5

• Furthermore, using both Northern blot analysis and reverse transcription-polymerase chain reaction, we have shown a reduced expression of Tlr5 during infection of MOLF/Ei mice with Salmonella [1].
• Flagellin is secreted by many enteric bacteria and, upon reaching the basolateral membrane of the intestinal epithelium, activates Toll-like receptor 5-mediated innate immune signaling pathways [2].
• Flagellin, the principal component of bacterial flagella, is a ligand for Toll-like receptor 5 (TLR5) or TLR11 and contributes to systemic inflammation during sepsis through activation of dendritic cells (DCs) and other cells of the innate immune system [3].
• Immunity to Legionella did not require MyD88, an essential adaptor for toll-like receptor 5 (TLR5) signaling [4].

High impact information on Tlr5

• Notably, transport of pathogenic Salmonella typhimurium from the intestinal tract to mesenteric lymph nodes was impaired in Tlr5-/- mice [5].
• Thus, detection of flagellin through Ipaf induces caspase-1 activation independently of Toll-like receptor 5 in salmonella-infected and lipopolysaccharide-tolerized macrophages [6].
• Delivery of flagellin to the macrophage cytosol induced Ipaf-dependent activation of caspase-1 that was independent of Toll-like receptor 5, required for recognition of extracellular flagellin [6].
• Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells [5].
• The dominant antigens identified were flagellins, molecules known to activate innate immunity via Toll-like receptor 5 (TLR5), and critical targets of the acquired immune system in host defense [7].

Biological context of Tlr5

• The presence of a quantitative trait locus for susceptibility to Salmonella typhimurium on distal chromosome 1 prompted the examination of Tlr5 in susceptible MOLF/Ei mice [1].
• Polymorphic sequence variants in Tlr5 allowed us to identify a unique 4-allele haplotype in MOLF/Ei [1].
• It thus appears that macrophages sense cytosolic flagellin via a TLR5-independent pathway that leads to rapid caspase-1-dependent cell death and provides defense against intracellular bacterial pathogens [4].

Anatomical context of Tlr5

• Although flagellin activation of the IL-1R-associated kinase and induction of TNF-alpha synthesis are dependent on TLR5 and not TLR4, we have found that flagellin stimulates NO in macrophages via a pathway that requires TLR5 and TLR4 [8].
• Recent work showed that flagellin, the monomeric subunit of bacterial flagella, triggers innate immune responses mediated by Toll-like receptor 5 [9].
• Therefore, like the recognition site of the innate immune receptor Toll-like receptor 5, three of four FliC epitopes recognized by CD4+ T cells colocalize in the D0/D1 domains of FliC [10].

Physical interactions of Tlr5

• Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes [8].

Analytical, diagnostic and therapeutic context of Tlr5

• Northern blot analysis reveals that Tlr5 is expressed predominantly in liver and lung with low-level expression in most other tissues examined [1].

References