title: Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands.
abstract: The secretory activity of Paneth cells is related to the bacterial milieu in the small intestine; however, the molecules involved in inducing Paneth cell secretion of enzymes and antimicrobial peptides are not well-defined. Mice treated orally with CpG-oligodeoxynucleotide (ODN), an agonist of Toll-like receptor (TLR) 9, showed rapid and massive Paneth cell degranulation. CpG-ODN-induced degranulation was not observed in TLR9(-/-) mice or in chimeric TLR9(-/-) mice reconstituted with wild-type (WT) bone marrow, but was observed in WT mice reconstituted with TLR9(-/-) bone marrow, indicating a role for TLR9-expressing gastrointestinal cells in CpG recognition. The TLR3 agonist polyinosinic-polycytidylic acid also induced rapid degranulation, whereas the TLR4 and TLR5 agonists LPS and flagellin, respectively, induced late degranulation mediated by TNF-α. Our evidence that TLR9 and TLR3 agonists induce Paneth cell degranulation points to the need for further studies of the mechanisms underlying Paneth cell function as an avenue toward preventing infection and treating inflammatory bowel diseases.
authors.affiliation: Department of Human Morphology and Biomedical Sciences Città Studi University of Milan, Milan, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.forename: Michele
authors.initials: M
authors.lastname: Sommariva
authors.forename: Lucia
authors.initials: L
authors.lastname: Sfondrini
authors.forename: Marco
authors.initials: M
authors.lastname: Palazzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Morelli
authors.forename: Laura
authors.initials: L
authors.lastname: Viganò
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology*; D005408:Flagellin / Q000494:pharmacology; D020381:Interleukin-17 / Q000378:metabolism; D007583:Jejunum / Q000166:cytology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D019879:Paneth Cells / Q000166:cytology / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000502:physiology*; D051198:Toll-Like Receptor 5 / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C408982:CPG-oligonucleotide; D020381:Interleukin-17; D008024:Ligands; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin