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Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9

A Marijke Keestra1, Marcel R de Zoete, Lieneke I Bouwman

  • 1Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)
|May 26, 2010
PubMed

Insights

Chicken TLR21 (chTLR21), a novel Toll-like receptor, recognizes CpG DNA, similar to mammalian TLR9. This finding reveals conserved ligand recognition across distantly related TLRs, expanding our understanding of innate immunity evolution.

Area of Science:

  • Immunology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Toll-like receptors (TLRs) are crucial for innate immunity, recognizing diverse microbial ligands.
  • The ligands for a major evolutionary branch of TLRs remain largely unidentified.
  • Chicken TLR21 (chTLR21) belongs to this understudied TLR group.

Purpose of the Study:

  • To clone and characterize the function of chicken TLR21 (chTLR21).
  • To investigate the ligand specificity and cellular localization of chTLR21.
  • To compare the function of chTLR21 with mammalian TLR9.

Main Methods:

  • Cloning and expression of chTLR21 in HEK293 cells.
  • NF-kappaB activation assays in response to various DNA and LPS stimuli.
  • Gene silencing of chTLR21 in chicken macrophages.
  • Confocal microscopy for subcellular localization.
  • Functional assays using chloroquine to inhibit endolysosomal maturation.

Main Results:

  • chTLR21 expression activated NF-kappaB in response to unmethylated CpG DNA.
  • Silencing chTLR21 in chicken macrophages abrogated CpG-DNA response.
  • chTLR21 recognized bacterial genomic DNA from Salmonella enterica.
  • chTLR21 localized to endolysosomes, similar to human TLR9.
  • chTLR21 responded to human and murine TLR9 ligands.

Conclusions:

  • Chicken TLR21 functions as an innate immune receptor recognizing CpG DNA.
  • chTLR21 shares functional and localization similarities with mammalian TLR9 despite distant phylogenetic relation.
  • This suggests convergent evolution of ligand recognition mechanisms in TLRs.

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