title: REG3γ-deficient mice have altered mucus distribution and increased mucosal inflammatory responses to the microbiota and enteric pathogens in the ileum.
abstract: REG3γ is considered to have a protective role against infection with Gram-positive bacteria due to its bactericidal activity, but evidence from in vivo studies is lacking. We generated a REG3γ(-/-) mouse, and investigated the effect of lack of REG3γ on intestinal mucus distribution, spatial compartmentalization of bacteria, and expression of innate immunity genes. Infection studies were also performed with Gram-positive and Gram-negative pathogens to investigate the antimicrobial role of REG3γ. REG3γ(-/-) mice display altered mucus distribution, increased bacterial contact with the epithelium, and elevated inflammatory markers in the ileum without histological evidence of pathology. Infection response pathway genes were differentially expressed in both Listeria monocytogenes and Salmonella enteritidis infected REG3γ(-/-) and wild-type (wt) mice. Higher amounts of myeloperoxidase and interleukin-22 transcripts were present in the ileal mucosa of REG3γ(-/-) than wt mice, but translocation to the organs was unaffected. We concluded that REG3γ has a protective role against mucosal infection with pathogenic Listeria and Salmonella in vivo. REG3γ is equally distributed throughout the mucus and its absence results in increased epithelial contact with the microbiota resulting in low-grade inflammation. REG3γ can bind to Gram-negative and Gram-positive bacteria and influence mucus distribution in the ileum, properties which may contribute to mucosal protection.
authors.affiliation: 1] TI Food and Nutrition, Wageningen, The Netherlands [2] Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: L M P
authors.initials: LM
authors.lastname: Loonen
authors.affiliation: Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Stolte
authors.affiliation: Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: M T J
authors.initials: MT
authors.lastname: Jaklofsky
authors.affiliation: Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Meijerink
authors.affiliation: TI Food and Nutrition, Wageningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Dekker
authors.affiliation: Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van Baarlen
authors.affiliation: 1] TI Food and Nutrition, Wageningen, The Netherlands [2] Host-Microbe Interactomics group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Wells
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007082:Ileum / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008089:Listeria monocytogenes / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D009093:Mucus / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012477:Salmonella enteritidis / Q000502:physiology; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D050835:Interferon Regulatory Factors; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D051196:Toll-Like Receptor 3; D007372:Interferons