PUBLICATION

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

Authors
Brugman, S., Schneeberger, K., Witte, M., Klein, M.R., van den Bogert, B., Boekhorst, J., Timmerman, H.M., Boes, M.L., Kleerebezem, M., Nieuwenhuis, E.E.
ID
ZDB-PUB-141224-7
Date
2014
Source
Gut microbes   5(6): 737-47 (Journal)
Registered Authors
Witte, Merlijn
Keywords
Lymphocytes / Microbiota / Mucosal immunity / Vibrio / Zebrafish, wpf: weeks post fertilization
MeSH Terms
  • Adaptive Immunity
  • Animals
  • Bacteria/classification
  • Bacteria/genetics
  • Bacteria/growth & development
  • Bacteria/isolation & purification
  • Disease Models, Animal
  • Gastrointestinal Tract/immunology
  • Gastrointestinal Tract/microbiology*
  • Humans
  • Immunity, Innate
  • T-Lymphocytes/immunology*
  • Vibrio/classification
  • Vibrio/growth & development*
  • Vibrio/immunology
  • Vibrio/isolation & purification
  • Vibrio Infections/immunology
  • Vibrio Infections/microbiology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/microbiology*
PubMed
25536157 Full text @ Gut Microbes
Abstract
Abstract Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping