IFNs Activate Toll-Like Receptor Gene Expression in Viral Infections

Genes Immun. 2001 Oct;2(6):349-55. doi: 10.1038/sj.gene.6363791.

Abstract

Toll-like receptors (TLRs) mediate innate immune responses to microbes. TLR2, TLR5, TLR6, and TLR9 have been implicated in responses to bacterial components, and TLR4 is the receptor for Gram-negative bacteria. Recently, TLR4 was described to function in respiratory syncytial virus-induced NF-kappaB activation. Here we have analyzed TLR1-9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses. TLR1, TLR2, TLR4, TLR6, and TLR8 mRNAs were expressed at basal levels in macrophages. Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression, and neutralizing anti-IFN-alpha/beta antibodies downregulated gene expression of these TLRs. Exogenously added IFN-alpha upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines. IFN-gamma enhanced the expression of TLR1 and TLR2 mRNA in macrophages, and TLR3 in epithelial and endothelial cells. The data suggests a novel role for IFNs in the activation of innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drosophila Proteins*
  • Humans
  • Influenza A virus / physiology*
  • Interferons / antagonists & inhibitors
  • Interferons / immunology
  • Interferons / metabolism*
  • Macrophages / metabolism*
  • Macrophages / virology*
  • Membrane Glycoproteins / genetics*
  • Neutralization Tests
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sendai virus / physiology*
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Up-Regulation*

Substances

  • Antibodies
  • Drosophila Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR3 protein, human
  • TLR4 protein, human
  • TLR5 protein, human
  • TLR7 protein, human
  • TLR8 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Interferons