Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1

J Leukoc Biol. 2010 Aug;88(2):227-32. doi: 10.1189/jlb.0809550. Epub 2010 Mar 18.

Abstract

In the present study, we dissected the pathways that trigger the IL-17A responses by MTB. Dectin-1 and TLR4 were shown to be involved in MTB-induced IL-17A production, and blockade of the NOD2, TLR2, or MR had no effect on IL-17A. The MAPK Erk, known to mediate transcription of IL-1beta mRNA, was strongly involved in the IL-17A production induced by MTB. The intracellular enzymes caspase-1 and serine proteases, which process pro-IL-1beta into the active IL-1beta, were also crucial for the induction of IL-17A. Lastly, the MTB-induced IL-17A response was strongly dependent on signaling through the IL-1R but not the IL-6R pathway. In conclusion, the MTB-induced IL-17A response relies strongly on the endogenous IL-1 pathway and IL-1R signaling. TLR4 and dectin-1 are the main receptors responsible for mediating the signals responsible for IL-17A production by MTB. These findings contribute to a better understanding of the host response to mycobacteria and provide the opportunity to explore potential, novel, therapeutic strategies against TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interleukin-1 / metabolism*
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology
  • Lectins, C-Type
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Nerve Tissue Proteins / metabolism*
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Interleukin-1
  • Interleukin-17
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Interleukin-1
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • dectin 1