Abstract
The release of antimicrobial peptides and growth factors by Paneth cells is thought to play an important role in protecting the small intestine, but the mechanisms involved have remained obscure. Immunohistochemistry and immunofluorescence showed that Paneth cells express Toll-like receptor 9 (TLR9) in the granules. Injection of mice with oligonucleotides containing CpG sequence (CpG-ODNs) led to a down-modulation of TLR9 and a striking decrease in the number of large secretory granules, consistent with degranulation. Moreover CpG-ODN treatment increased resistance to oral challenge with virulent Salmonella typhimurium. Moreover, our findings demonstrate a sentinel role for Paneth cells through TLR9.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Animals
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Cells, Cultured
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Cytoplasmic Granules / drug effects
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Cytoplasmic Granules / metabolism*
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Cytoplasmic Granules / pathology
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DNA-Binding Proteins / metabolism*
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Fluorescent Antibody Technique
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Humans
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Immunoenzyme Techniques
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Intestine, Small / drug effects
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Intestine, Small / metabolism*
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Intestine, Small / microbiology
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Mice
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Mice, Inbred C57BL
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Oligodeoxyribonucleotides / pharmacology*
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Paneth Cells / drug effects
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Paneth Cells / metabolism*
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Paneth Cells / microbiology
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Receptors, Cell Surface / metabolism*
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Salmonella Infections, Animal / metabolism
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Salmonella Infections, Animal / pathology
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Salmonella typhimurium / pathogenicity
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Secretory Vesicles / drug effects
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Secretory Vesicles / metabolism*
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Secretory Vesicles / pathology
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Survival Rate
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Toll-Like Receptor 9
Substances
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Adjuvants, Immunologic
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CPG-oligonucleotide
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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Receptors, Cell Surface
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TLR9 protein, human
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Tlr9 protein, mouse
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Toll-Like Receptor 9