Roles of Toll-Like Receptor 4 and IL-23 in IL-17 Expression in Response to Klebsiella pneumoniae Infection

• Published in: The Journal of immunology (1950) Vol. 170; no. 9; pp. 4432 - 4436
• Main Authors: Happel, KI, Zheng, M, Young, E, Quinton, L J, Lockhart, E, Ramsay, A J, Shellito, JE, Schurr, J R, Bagby, G J, Nelson, S, Kolls, J K
• Format: Journal Article
• Language: English
• Published: 01.05.2003
• ISSN: 0022-1767

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 super(+) T cell product, we also demonstrate significant in vitro IL-17 production by CD8 super(+) 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 super(+) and CD8 super(+) 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 super(+) T cell IL-17 production.