Microbial Colonization in Adulthood Shapes the Intestinal Macrophage Compartment.
Age Factors
Animals
Colitis
/ chemically induced
Dextran Sulfate
/ pharmacology
Flow Cytometry
Fluorescent Antibody Technique
Gastrointestinal Microbiome
/ genetics
Germ-Free Life
Ileum
/ cytology
Intestinal Mucosa
/ cytology
Macrophages
/ physiology
Male
Mice
Mice, Inbred C3H
RNA, Ribosomal, 16S
/ genetics
Specific Pathogen-Free Organisms
DSS colitis
Microbial colonization
intestinal macrophages
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
19 Sep 2019
19 Sep 2019
Historique:
pubmed:
3
4
2019
medline:
13
2
2020
entrez:
3
4
2019
Statut:
ppublish
Résumé
Contact with distinct microbiota early in life has been shown to educate the mucosal immune system, hence providing protection against immune-mediated diseases. However, the impact of early versus late colonization with regard to the development of the intestinal macrophage compartment has not been studied so far. Germ-free mice were colonized with specific-pathogen-free [SPF] microbiota at the age of 5 weeks. The ileal and colonic macrophage compartment were analysed by immunohistochemistry, flow cytometry, and RNA sequencing 1 and 5 weeks after colonization and in age-matched SPF mice, which had had contact with microbiota since birth. To evaluate the functional differences, dextran sulfate sodium [DSS]-induced colitis was induced, and barrier function analyses were undertaken. Germ-free mice were characterized by an atrophied intestinal wall and a profoundly reduced number of ileal macrophages. Strikingly, morphological restoration of the intestine occurred within the first week after colonization. In contrast, ileal macrophages required 5 weeks for complete restoration, whereas colonic macrophages were numerically unaffected. However, following DSS exposure, the presence of microbiota was a prerequisite for colonic macrophage infiltration. One week after colonization, mild colonic inflammation was observed, paralleled by a reduced inflammatory response after DSS treatment, in comparison with SPF mice. This attenuated inflammation was paralleled by a lack of TNFα production of LPS-stimulated colonic macrophages from SPF and colonized mice, suggesting desensitization of colonized mice by the colonization itself. This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Contact with distinct microbiota early in life has been shown to educate the mucosal immune system, hence providing protection against immune-mediated diseases. However, the impact of early versus late colonization with regard to the development of the intestinal macrophage compartment has not been studied so far.
METHODS
METHODS
Germ-free mice were colonized with specific-pathogen-free [SPF] microbiota at the age of 5 weeks. The ileal and colonic macrophage compartment were analysed by immunohistochemistry, flow cytometry, and RNA sequencing 1 and 5 weeks after colonization and in age-matched SPF mice, which had had contact with microbiota since birth. To evaluate the functional differences, dextran sulfate sodium [DSS]-induced colitis was induced, and barrier function analyses were undertaken.
RESULTS
RESULTS
Germ-free mice were characterized by an atrophied intestinal wall and a profoundly reduced number of ileal macrophages. Strikingly, morphological restoration of the intestine occurred within the first week after colonization. In contrast, ileal macrophages required 5 weeks for complete restoration, whereas colonic macrophages were numerically unaffected. However, following DSS exposure, the presence of microbiota was a prerequisite for colonic macrophage infiltration. One week after colonization, mild colonic inflammation was observed, paralleled by a reduced inflammatory response after DSS treatment, in comparison with SPF mice. This attenuated inflammation was paralleled by a lack of TNFα production of LPS-stimulated colonic macrophages from SPF and colonized mice, suggesting desensitization of colonized mice by the colonization itself.
CONCLUSIONS
CONCLUSIONS
This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.
Identifiants
pubmed: 30938416
pii: 5425556
doi: 10.1093/ecco-jcc/jjz036
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1173-1185Informations de copyright
Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.For permissions, please email: journals.permissions@oup.com.