title: Lactobacillus rhamnosus GG increases Toll-like receptor 3 gene expression in murine small intestine ex vivo and in vivo.
abstract: Administration of Lactobacillus rhamnosus GG (LGG) has been reported to be therapeutically effective against acute secretory diarrhoea resulting from the structural and functional intestinal mucosal lesions induced by rotavirus infection; however, the underlying mechanisms remain to be completely elucidated. Because Toll-like receptor 3 (TLR3) plays a key role in the innate immune responses following the recognition of rotavirus, the present study examined whether LGG influences TLR3 gene expression in murine small intestine ex vivo and in vivo. We employed cultured intestinal organoids derived from small intestinal crypts as an ex vivo tissue model. LGG supplementation increased TLR3 mRNA levels in the intestinal organoids, as estimated by quantitative real-time polymerase chain reaction. Likewise, single and 7-day consecutive daily administrations of LGG increased TLR3 mRNA levels in the small intestine of C57BL/6N mice. The mRNA levels of other TLRs were not substantially altered both ex vivo and in vivo. In addition, LGG supplementation increased the mRNA levels of an antiviral type 1 interferon, interferon-α (IFN-α), and a neutrophil chemokine, CXCL1, upon stimulation with a synthetic TLR3 ligand, poly(I:C) in the intestinal organoids. LGG administration did not alter IFN-α and CXCL1 mRNA levels in the small intestine in vivo. Supplementation of other bacterial strains, Bifidobacterium bifidum and Lactobacillus paracasei, failed to increase TLR3 and poly(I:C)-stimulated CXCL1 mRNA levels ex vivo. We propose that upregulation of TLR3 gene expression may play a pivotal role in the therapeutic efficacy of LGG against rotavirus-associated diarrhoea. In addition, we demonstrated that intestinal organoids may be a promising ex vivo tissue model for investigating host-pathogen interactions and the antiviral action of probiotics in the intestinal epithelium.
authors.affiliation: 1 Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.|2 Division of Fundamental AgriScience Research, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Aoki-Yoshida
authors.affiliation: 2 Division of Fundamental AgriScience Research, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.affiliation: 2 Division of Fundamental AgriScience Research, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukiya
authors.affiliation: 3 Functional Biomolecules Research Group, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Aoki
authors.affiliation: 3 Functional Biomolecules Research Group, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: 3 Functional Biomolecules Research Group, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Suzuki
authors.affiliation: 2 Division of Fundamental AgriScience Research, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sonoyama
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D007421:Intestine, Small / Q000473:pathology*; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009940:Organoids; D019936:Probiotics / Q000008:administration & dosage*; D060888:Real-Time Polymerase Chain Reaction; D012400:Rotavirus Infections / Q000473:pathology* / Q000517:prevention & control*; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*
chemical_list: D051196:Toll-Like Receptor 3
keywords: CXCL1; interferon-α; intestinal organoids; probiotics; rotavirus