J Neurogastroenterol Motil.  2011 Jan;17(1):28-34.

Basic and Translational Understandings of Microbial Recognition by Toll-Like Receptors in the Intestine

Affiliations
  • 1Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. shrhee@mednet.ucla.edu

Abstract

Microbial recognition by multicellular organisms is initially accomplished by a group of pattern recognition receptors which are specialized to recognize microbe-associated molecular patterns (MAMPs) such as lipopolysaccharide, bacterial lipoprotein, CpG DNA motif, double strand RNA and flagellin. Toll-like receptors (TLRs) are the representative pattern recognition receptors, and microbial recognition by TLRs elicits innate and inflammatory responses. Ten TLR family members have been presently identified in human genome, and numerous studies discovered that intracellular responses from MAMPs-TLR engagements are mediated by a participation of at least 4 immediate adaptor molecules such as myeloid differentiation primary response gene-88 (MyD88), MyD88 adaptor-like (Mal) (also known as Toll/IL-1 receptor domain-containing adaptor protein [TIRAP]), Toll/IL-1 receptor domain-containing adaptor-inducing interferon-beta (TRIF) and TRIF-related adaptor molecule (TRAM) leading to activate transcription factors including nuclear factor kappaB, activator protein-1 and interferon-regulatory factors. Given that large amounts of commensal microbiota constantly reside in the intestinal lumen, enteric microbial recognition by TLRs at the intestinal epithelium provides a critical impact on regulating intestinal homeostasis. Indeed, aberrant TLR4 and TLR5 activations are etiologically associated with the development and progress of intestinal inflammatory diseases including inflammatory bowel disease and necrotizing enterocolitis. In this review article, we present the molecular mechanism by which TLRs elicit intracellular signal transduction, and summarize the physiological relevance of TLRs related to the gastrointestinal tract.

Keyword

Flagellin; Immunity, innate; Toll-like receptor

MeSH Terms

Enterocolitis, Necrotizing
Flagellin
Gastrointestinal Tract
Genome, Human
Homeostasis
Humans
Immunity, Innate
Inflammatory Bowel Diseases
Interferon-beta
Intestinal Mucosa
Intestines
Lipoproteins
Metagenome
Nucleotide Motifs
Receptors, Pattern Recognition
RNA
Signal Transduction
Toll-Like Receptors
Transcription Factor AP-1
Transcription Factors
Flagellin
Interferon-beta
Lipoproteins
RNA
Receptors, Pattern Recognition
Toll-Like Receptors
Transcription Factor AP-1
Transcription Factors
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