Abstract
How the development of antibacterial T helper 17 (Th17) cells is selectively promoted by antigen-presenting dendritic cells (DCs) is unclear. We showed that bacteria, but not viruses, primed human DCs to promote IL-17 production in memory Th cells through the nucleotide oligomerization domain 2 (NOD2)-ligand muramyldipeptide (MDP), a derivative of bacterial peptidoglycan. MDP enhanced obligate bacterial Toll-like receptor (TLR) agonist induction of IL-23 and IL-1, which promoted IL-17 expression in T cells. The role of NOD2 in this IL-23-IL-1-IL-17 axis could be confirmed in NOD2-deficient DCs, such as DCs from selected Crohn's disease patients. Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP.
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / immunology
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Animals
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Antigen Presentation / immunology
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Bacterial Infections / immunology*
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Crohn Disease / genetics
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Crohn Disease / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Enzyme-Linked Immunosorbent Assay
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Humans
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Immunologic Memory*
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Interleukin-1 / immunology
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Interleukin-12 / immunology
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Interleukin-17 / biosynthesis*
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Interleukin-17 / immunology
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Lymphocyte Activation / immunology
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Mice
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Nod2 Signaling Adaptor Protein / immunology*
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Nod2 Signaling Adaptor Protein / metabolism
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RNA, Messenger
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RNA, Small Interfering
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Interleukin-1
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Interleukin-17
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NOD2 protein, human
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Nod2 Signaling Adaptor Protein
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RNA, Messenger
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RNA, Small Interfering
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Interleukin-12
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Acetylmuramyl-Alanyl-Isoglutamine