Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections

Tomasz Ahrends, Begüm Aydin, Fanny Matheis, Cajsa H. Classon, François Marchildon, Gláucia C. Furtado, Sérgio A. Lira, Daniel Mucida

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss, dysmotility, and maintains energy balance during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via β2-adrenergic receptors (β2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and IL-13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease or tissue tolerance that preserves ENS number and functionality.

Original languageEnglish
Pages (from-to)5715-5727.e12
JournalCell
Volume184
Issue number23
DOIs
StatePublished - 11 Nov 2021

Keywords

  • enteric infections
  • enteric neurons
  • eosinophils
  • macrophages
  • neuroimmunology
  • small intestine

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