Cholinergic receptor-Wnt pathway controls immune activation by sensing intestinal dysfunction

Jie Ren, Yu Sang, Alejandro Aballay

Research output: Contribution to journalArticlepeer-review

Abstract

Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection. ACC-4 acts postsynaptically in non-cholinergic RIM neurons to regulate several immune genes and a Wnt-mediated host immune response. These findings uncover a gut-brain-microbial axis that uses neural cholinergic signaling and the Wnt pathway to control immune activation in response to alterations in intestinal homeostasis.

Original languageEnglish (US)
Article number111575
JournalCell Reports
Volume41
Issue number5
DOIs
StatePublished - Nov 1 2022

Keywords

  • ACC-4
  • C. elegans
  • CP: Immunology
  • RIM neuron
  • Wnt
  • acetylcholine
  • cholinergic receptor
  • intestinal distension

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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