A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system developmentReportar como inadecuado




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BMC Genomics

, 13:335

Transcriptomic methods

Abstract

BackgroundEpidemiological studies have suggested that the encounter with commensal microorganisms during the neonatal period is essential for normal development of the host immune system. Basic research involving gnotobiotic mice has demonstrated that colonization at the age of 5 weeks is too late to reconstitute normal immune function. In this study, we examined the transcriptome profiles of the large intestine LI, small intestine SI, liver LIV, and spleen SPL of 3 bacterial colonization models—specific pathogen- free mice SPF, ex-germ-free mice with bacterial reconstitution at the time of delivery 0WexGF, and ex-germ-free mice with bacterial reconstitution at 5 weeks of age 5WexGF—and compared them with those of germ-free GF mice.

ResultsHundreds of genes were affected in all tissues in each of the colonized models; however, a gene set enrichment analysis method, MetaGene Profiler MGP, demonstrated that the specific changes of Gene Ontology GO categories occurred predominantly in 0WexGF LI, SPF SI, and 5WexGF SPL, respectively. MGP analysis on signal pathways revealed prominent changes in toll-like receptor TLR- and type 1 interferon IFN-signaling in LI of 0WexGF and SPF mice, but not 5WexGF mice, while 5WexGF mice showed specific changes in chemokine signaling. RT-PCR analysis of TLR-related genes showed that the expression of interferon regulatory factor 3 Irf3, a crucial rate-limiting transcription factor in the induction of type 1 IFN, prominently decreased in 0WexGF and SPF mice but not in 5WexGF and GF mice.

ConclusionThe present study provides important new information regarding the molecular mechanisms of the so-called -hygiene hypothesis-.

KeywordsHygiene hypothesis Germ-free Toll-like receptor Type 1 interferon MetaGene Profiler Abbreviations0WexGFGerm-free mice with bacterial reconstitution at the time of delivery

5WexGFGerm-free mice with bacterial reconstitution at 5 weeks of age

BPBiological Process

CCCellular Component

GFGerm-free

GOGene Ontology

GSEAGene set enrichment analysis

IFNInterferon

ILInterleukin

LILarge intestine

MFMolecular Function

MGPMetaGene Profiler

SISmall intestine

SPFSpecific pathogen free

ThT helper

TLRToll like receptor

TregRegulatory T.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-13-335 contains supplementary material, which is available to authorized users.

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Autor: Masahiro Yamamoto - Rui Yamaguchi - Kaori Munakata - Kiyoe Takashima - Mitsue Nishiyama - Kyoji Hioki - Yasuyuki Ohnishi -

Fuente: https://link.springer.com/



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