Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection

J Immunol. 2003 May 1;170(9):4432-6. doi: 10.4049/jimmunol.170.9.4432.

Abstract

Local production of IL-17 is a significant factor in effective host defense against Gram-negative bacteria. However, the proximal events mediating IL-17 elaboration by T cells remain unclear. In this study, we show in vivo that intact Toll-like receptor 4 signaling in the lung is required for induction of both the p19 transcript of IL-23 and IL-17 protein elaboration in response to Klebsiella pneumoniae. Although IL-17 is widely considered a CD4(+) T cell product, we also demonstrate significant in vitro IL-17 production by CD8(+) T cells after culture in medium from dendritic cells exposed to these bacteria. The dominant portion of this IL-17-inducing activity for both CD4(+) and CD8(+) T cells is IL-23. These data demonstrate the critical signaling pathway for IL-17 induction in the host response to Gram-negative pulmonary infection and suggest a direct role for IL-23 in CD8(+) T cell IL-17 production.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Coculture Techniques
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / genetics
  • Interleukins / physiology*
  • Klebsiella Infections / immunology*
  • Klebsiella Infections / metabolism
  • Klebsiella pneumoniae / immunology*
  • Lung / immunology
  • Lung / metabolism
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Subunits / genetics
  • Protein Subunits / physiology
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / physiology*
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Toll-Like Receptors

Substances

  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Membrane Glycoproteins
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptors