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| Status |
Public on Feb 21, 2022 |
| Title |
A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter’s contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter inducing interferon-b (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-b reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit, and leukocyte extravasation into the ME. TRIF/ TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry, and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.
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| Overall design |
Examination of MHCII+ CX3CR1- and MHCII+ CX3CR1+ cells isolated from the muscularis externa of the small bowel
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| Contributor(s) |
Enderes J, Hupa KJ, Günther P, Schultze JL, Wehner S |
| Citation(s) |
33519804 |
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| Submission date |
Jun 03, 2019 |
| Last update date |
Feb 21, 2022 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
[email protected]
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| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
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| Department |
Genomics and Immunoregulation
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| Street address |
Carl-Troll-Strasse 31
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| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (6)
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| GSM3847617 |
CX3CR1_pos dendritic cells (Sample_2040) |
| GSM3847618 |
CX3CR1_neg dendritic cells (Sample_2041) |
| GSM3847619 |
CX3CR1_neg dendritic cells (Sample_2043) |
| GSM3847620 |
CX3CR1_pos dendritic cells (Sample_2044) |
| GSM3847621 |
CX3CR1_pos dendritic cells (Sample_2046) |
| GSM3847622 |
CX3CR1_neg dendritic cells (Sample_2047) |
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| Relations |
| BioProject |
PRJNA546030 |
| SRA |
SRP200294 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132147_Normalized-processed_RNA-seq_data.txt.gz |
794.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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