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

KI Happel, M Zheng, E Young, LJ Quinton… - The Journal of …, 2003 - journals.aai.org
KI Happel, M Zheng, E Young, LJ Quinton, E Lockhart, AJ Ramsay, JE Shellito, JR Schurr…
The Journal of Immunology, 2003journals.aai.org
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 …
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.
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