title: T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut.
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.
authors.affiliation: a Department of Paediatric Gastroenterology, Wilhelmina Children's Hospital , University Medical Centre Utrecht , Utrecht , The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Brugman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schneeberger
authors.forename: Merlijn
authors.initials: M
authors.lastname: Witte
authors.forename: Mark R
authors.initials: MR
authors.lastname: Klein
authors.forename: Bartholomeus
authors.initials: B
authors.lastname: van den Bogert
authors.forename: Jos
authors.initials: J
authors.lastname: Boekhorst
authors.forename: Harro M
authors.initials: HM
authors.lastname: Timmerman
authors.forename: Marianne L
authors.initials: ML
authors.lastname: Boes
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate; D013601:T-Lymphocytes / Q000276:immunology*; D014733:Vibrio / Q000145:classification / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D014735:Vibrio Infections / Q000276:immunology / Q000382:microbiology*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*
keywords: lymphocytes, microbiota, mucosal immunity, Vibrio, zebrafish; wpf: weeks post fertilization