Abstract

BackgroundAlthough microbiota play a critical role in the normal development and function of host immune systems, the underlying mechanisms, especially those involved in the large intestine (LI), remain unknown. In the present study, we performed transcriptome analysis of the LI of germ-free (GF) and specific pathogen-free (SPF) mice of the IQI strain, an inbred strain established from ICR mice.ResultsGeneChip analysis, quantitative real-time RT-PCR, and reconfirmation using bacteria-inoculated GF mice revealed differences in the expression levels of several immune-related genes, such as cryptdin-related sequences (CRS), certain subsets of type 1 interferon (IFN)-related genes, class Ib MHC molecules, and certain complements. LI expressed no authentic cryptdins but predominantly expressed CRS2, 4, and 7. The mRNA levels of IFN-related genes, including Irf7, Isgf3g, Ifit1 and Stat1, were lower in SPF- and flora-reconstituted mice. When an oral IFN-α inducer tilorone analog, R11567DA, was administered to SPF mice, IFN-α was induced rapidly in the LI at 4 h, whereas no IFN-α protein was detected in the small intestine (SI) or blood. In situ hybridization and immunohistochemistry suggested that the IFN-α production originated from Paneth cells in the SI, and portions of lamina proprial CD11b- or mPDCA1-positive cells in the LI.ConclusionThe present study suggests that microbial colonization, while inducing the expression of anti-microbial peptides, results in the down-regulation of certain genes responsible for immune responses, especially for type I IFN synthesis. This may reflect the adaptation process of the immune system in the LI to prevent excessive inflammation with respect to continuous microbial exposure. Further, the repertoire of anti-microbial peptides and the extraordinary role of interferon producing cells in the LI have been found to be distinct from those in the SI.

Highlights

  • Microbiota play a critical role in the normal development and function of host immune systems, the underlying mechanisms, especially those involved in the large intestine (LI), remain unknown

  • When we applied the same criteria, there were 43 probe sets expressed at lower levels in specific pathogen-free (SPF) mice than in GF mice (Table 2)

  • Previous transcriptome studies that have focused on intestinal epithelial cells (IECs) [20,28] did not appear to adequately characterize the microflora-induced immunological changes in terms of transcriptional profiling, even in the small IECs, the physiology of which is supposed to be profoundly affected by a variety of GALT-derived cells and/or mediators

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Summary

Introduction

Microbiota play a critical role in the normal development and function of host immune systems, the underlying mechanisms, especially those involved in the large intestine (LI), remain unknown. Intestinal flora have been suggested to play a critical role in the normal development and physiology of host animals. The immune response must be balanced between defending against pathogens while at the same time recognizing commensals as harmless [1,2,3]. The normal colon, apparently lacks important structures/components such as Peyer's patches (PP) and Paneth cells, and little is known about the immunology of the large intestine, despite the marked differences in both function and luminal environment between the different regions of the intestine [6,7]

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