title: Three months of Western diet induces small intestinal mucosa alteration in TLR KO mice.
abstract: Several studies support the role of Western-style diet (WD) in inflammatory bowel disease (IBD). Toll-like receptors/NOD-like receptors (TLRs/NLRs) are important to maintain a healthy epithelium as well as inducing inflammation. Given that dietary factors influence IBD development, that epithelial dysfunction is thought to be involved in initiating intestinal inflammation and that TLR-NLR are involved in maintenance of the functionality of intestinal epithelium as well as in regulating inflammation, we decided to examine the role of TLR signals in the triggering events that lead to alteration of the small intestinal epithelium associated to consumption of WD. C57BL/6J mice deficient for TLR2, 4, 9, or NOD2 and wild-type (WT) were fed a WD or a standard diet for 3 months. The effects of WD on small intestinal samples were evaluated by histological and immunohistochemical analysis. After 3 months, WD modifies the morphology and the organization of the small intestine in TLR9 KO mice compared with WT mice and the others TLRs. The most interesting change involved the expression of proliferative and differentiation markers of WNT signaling, Ki67 and FzD5. Mice deficient in TLR2, 4, and NOD2 have a significant reduction in the proliferative cell numbers but do not show any signs of histological alterations. Our results suggest that TLR9 is an important protective factor in intestinal epithelial homeostasis and provide new insights into an unrecognized role of TLR9 signaling in the small intestinal mucosa dysfunction associated with WD.
authors.affiliation: Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sardi
authors.affiliation: Adaptive Immunity Lab, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Luchini
authors.affiliation: Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Emanuelli
authors.affiliation: Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Giannoni
authors.affiliation: Adaptive Immunity Lab, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martini
authors.affiliation: Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Manara
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, University of Milan, via Mangiagalli 31, Milan, 20133, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sfondrini
authors.affiliation: Adaptive Immunity Lab, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Italy.|Humanitas University, Via Manzoni 113, Rozzano, 20089, Italy.
authors.forename: Marinos
authors.initials: M
authors.lastname: Kallikourdis
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, University of Milan, via Mangiagalli 31, Milan, 20133, Italy.|Molecular Targets Unit, Fondazione IRCCS - Istituto nazionale dei Tumori, via Venezian 1, Milan, 20133, Italy.
authors.forename: Michele
authors.identifier: http://orcid.org/0000-0002-7622-0996
authors.initials: M
authors.lastname: Sommariva
authors.affiliation: Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
mesh_terms: D000818:Animals; D066273:Diet, Western / Q000009:adverse effects*; D051157:Frizzled Receptors / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D015430:Weight Gain / Q000502:physiology*
chemical_list: D051157:Frizzled Receptors; C403211:Fzd5 protein, mouse; D019394:Ki-67 Antigen; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
keywords: NLR; TLR; gut; high fat diet; mouse models; pathogen-recognition receptors