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(American Journal of Pathology. 2004;165:373-381.)
© 2004 American Society for Investigative Pathology

Degranulation of Paneth Cells via Toll-Like Receptor 9

Cristiano Rumio*, Dario Besusso{dagger}, Marco Palazzo*, Silvia Selleri*, Lucia Sfondrini{dagger}, Francesco Dubini{ddagger}, Sylvie Ménard{dagger} and Andrea Balsari§

From the Department of Human Morphology* and the Institutes of Microbiology{ddagger} and Pathology,§ University of Milan, Milan; and the Molecular Targeting Unit,{dagger} Istituto Nazionale Tumori, Milan, Italy

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.




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