Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections.
Cell
; 184(23): 5715-5727.e12, 2021 11 11.
Article
in En
| MEDLINE
| ID: mdl-34717799
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 ß2-adrenergic receptors (ß2AR) 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Organ Specificity
/
Yersinia pseudotuberculosis
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Enteric Nervous System
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Neuroprotection
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Infections
/
Neurons
Limits:
Animals
Language:
En
Year:
2021
Type:
Article