The flagellin-TLR5 axis: Therapeutic opportunities

Lucas Liaudet, Amitabha Deb, Pál Pacher, Jon G. Mabley, Kanneganti G.K. Murthy, Andrew L. Salzman, Csaba Szabó

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

Motile bacteria synthesize large-sized surface structures known as flagella through the ordered polymerization of protein subunits. Flagellin, a protein of 40-60 kDa, is the principal constituent of the flagellum; each flagellum consists of approximately 20,000 flagellin molecules. An alignment of the amino acid sequences from different Gram-negative species shows a high degree of similarity in the amino and carboxy terminal domains. In contrast, the central hypervariable regions of these proteins are quite divergent. Recent work reveals that - in addition to playing a role in bacterial adhesion - monomeric flagellin, a protein component of flagellated bacteria, can also act as a soluble immunostimulatory and proinflammatory factor, activating the immune/inflammatory axis via the Toll-like receptor 5-nuclear factor-κB axis. Monocytes and macrophages, as well as intestinal and pulmonary epithelial cells, respond to monomeric flagellin at low concentrations. Administration of flagellin at doses comparable to or lower than that of bacterial lipopolysaccharide (endotoxin) can induce prominent local and systemic immune/inflammatory responses in vivo. Recognition of the flagellin-TLR5 pathway offers novel opportunities for the experimental therapy of various forms of shock, sepsis, acute respiratory distress syndrome, bacterial inflammation and infection.

Original languageEnglish (US)
Pages (from-to)397-409
Number of pages13
JournalDrug News and Perspectives
Volume15
Issue number7
DOIs
StatePublished - Sep 2002
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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