title: Interleukin-13-mediated paneth cell degranulation and antimicrobial peptide release.
abstract: Paneth cell-derived enteric antimicrobial peptides significantly contribute to antibacterial host defense and host-microbial homeostasis. Regulation occurs by enzymatic processing and release into the small intestinal lumen, but the stimuli involved are incompletely understood. Here, the capacity of various microbial and immune stimuli to induce antimicrobial peptide release from small intestinal tissue was systematically evaluated using antibacterial activity testing, immunostaining for Paneth cell granules and mass spectrometry. We confirmed the stimulatory activity of the muscarinic receptor agonist carbachol and the nucleotide-binding oligomerization domain ligand muramyl dipeptide. In contrast, no release of antibacterial activity was noted after treatment with the Toll-like receptor ligands poly(I:C), lipopolysaccharide or CpG, and the cytokines interleukin (IL)-15, IL-22, IL-28 and interferon-γ. Rapid Paneth cell degranulation and antimicrobial activity release, however, was observed after stimulation with the endogenous mediators IL-4 and IL-13. This process required phosphatidylinositol 3-kinase and was associated with protein kinase B phosphorylation in Paneth cells. Flow cytometric analysis confirmed expression of the IL-13 receptor α1 on isolated Paneth cells. Our findings identify a novel role of IL-13 as inducer of Paneth cell degranulation and enteric antimicrobial peptide release. IL-13 may thus contribute to mucosal antimicrobial host defense and host microbial homeostasis.
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stockinger
authors.forename: Thorben
authors.initials: T
authors.lastname: Albers
authors.forename: Claudia U
authors.initials: CU
authors.lastname: Duerr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ménard
authors.forename: Katrin
authors.initials: K
authors.lastname: Pütsep
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D015550:Cell Degranulation; D002478:Cells, Cultured; D018928:Immunity, Mucosal; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D019879:Paneth Cells / Q000187:drug effects / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053660:Receptors, Interleukin-13 / Q000235:genetics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D018793:Interleukin-13; D053660:Receptors, Interleukin-13; D011976:Receptors, Muscarinic; D015847:Interleukin-4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D002217:Carbachol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt