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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Coculture Techniques
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Interleukin-17 / biosynthesis*
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Interleukin-17 / genetics
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins / genetics
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Interleukins / physiology*
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Klebsiella Infections / immunology*
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Klebsiella Infections / metabolism
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Klebsiella pneumoniae / immunology*
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Lung / immunology
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Lung / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Subunits / genetics
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Protein Subunits / physiology
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RNA, Messenger / biosynthesis
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Receptors, Cell Surface / physiology*
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Toll-Like Receptors
Substances
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Il23a protein, mouse
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Interleukin-17
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins
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Membrane Glycoproteins
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Protein Subunits
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RNA, Messenger
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Receptors, Cell Surface
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Toll-Like Receptors