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Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands

✍ Scribed by Cristiano Rumio; Michele Sommariva; Lucia Sfondrini; Marco Palazzo; Daniele Morelli; Laura Viganò; Loris De Cecco; Elda Tagliabue; Andrea Balsari


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
329 KB
Volume
227
Category
Article
ISSN
0021-9541

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✦ Synopsis


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. J. Cell. Physiol. 227: 1107–1113, 2012. © 2011 Wiley Periodicals, Inc.