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Status |
Public on Aug 17, 2021 |
Title |
Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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 and dysmotility during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via b2-adrenergic receptors (b2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and -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.
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Overall design |
C57BL/6J mice were s.c. injected with water (non-infected, NI) or infected with spiB, Sv or Yp. Ileum MMs were sorted for RNA-seq.
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Contributor(s) |
Ahrends T |
Citation(s) |
34717799 |
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Submission date |
Aug 17, 2021 |
Last update date |
Nov 16, 2021 |
Contact name |
Tomasz Ahrends |
Organization name |
The Rockefellere University
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Lab |
Mucosal Immunology
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Street address |
1230 York Ave
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10065 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA755704 |
SRA |
SRP332924 |