Intestinal microbiome adjusts the innate immune setpoint during colonization through negative regulation of MyD88

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  • Bjørn E.V. Koch, The Institute of Biology Leiden, Gorlaeus Laboratoria, Leiden University
  • ,
  • Shuxing Yang, The Institute of Biology Leiden, Gorlaeus Laboratoria, Leiden University, Chinese Academy of Sciences
  • ,
  • Gerda Lamers, The Institute of Biology Leiden, Gorlaeus Laboratoria, Leiden University
  • ,
  • Jens Stougaard
  • Herman P. Spaink, The Institute of Biology Leiden, Gorlaeus Laboratoria, Leiden University

Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.

Original languageEnglish
Article number4099
JournalNature Communications
Volume9
Issue1
Number of pages11
ISSN2041-1723
DOIs
Publication statusPublished - 1 Dec 2018

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