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| Status |
Public on Mar 12, 2024 |
| Title |
Epithelial relay of microbial signals coordinates intestinal macrophage supported barrier repair [E. coli strains] |
| Organism |
Escherichia coli |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The gastrointestinal tract is colonized by trillions of microorganisms collectively known as the gut microbiota. These microbes provide essential signals to support healthy gut function. The microbiota is separated from internal tissue by a single layer of intestinal epithelial cells that not only provides a physical barrier but also relays luminal signals to underlying gut immune cells. Altered microbiota composition including loss of anti-inflammatory microbes or outgrowth of mucosa-associated bacteria such as adherent-invasive E. coli (AIEC) are hallmarks of inflammatory disease including inflammatory bowel disease (IBD). In contrast to their hypothesized role in pathology, we recently identified select AIEC isolates that improve outcomes in mouse colitis models. These AIEC induce macrophage production of the anti-inflammatory cytokine IL-10 which limits gut inflammation and supports barrier repair. These benefits were lost if the AIEC was unable to attach to epithelial cells. However, the epithelial signaling underlying this protection remained unclear. To understand if intestinal epithelial cells signaled to immune cells after microbial attachment, we utilized human colonic organoid monolayers and found co-culture with a subset of AIEC isolates upregulated immune regulatory genes including CCL2, a macrophage recruiting chemokine. This effect was only observed in undifferenced epithelial cells, indicating epithelial stem cell recognition of microbes leads to macrophage recruitment. In vivo, antibody blockade of CCR2 abrogated the protective effect of AIEC colonization. Using bacterial transcriptome analysis, we identified high flagellin expression in AIEC isolates that activated epithelial signaling, with lost signaling in organoids deficient for TLR5, the receptor for flagellin. Together our findings suggest intestinal epithelial cells recognize microbial signals to coordinate macrophage recruitment that support intestinal repair, protecting from colitis.
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| Overall design |
We screened a panel of E. coli strains, which were isolated from mucosal biopsy as part of the human microbiome projec, using Caco2 cells to indentify strains that induces epithelial responses. Of the strains tested, about half induced upregulation of the epithelial immune response genes as 541-15. We grouped them as "activators" while we classified the rest as "non-activators". To identify the signature genes that specifically expressed by the activators or non-activators, we performed bacterial transctiptome profiling.
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| Contributor(s) |
Ming-Ting T, Gretchen D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 07, 2024 |
| Last update date |
Mar 12, 2024 |
| Contact name |
Ming-Ting Kessler Tsai |
| E-mail(s) |
kesslertsai@gmail.com
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Immunology
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| Lab |
Diehl
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| Street address |
408 E 69th Street Z1619
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL14548 |
Illumina HiSeq 2000 (Escherichia coli) |
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| Samples (34)
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| GSM8133394 |
E.coli, 2A, replicate2 |
| GSM8133395 |
E.coli, GDAR2-2, replicate1 |
| GSM8133396 |
E.coli, GDAR2-2, replicate2 |
| GSM8133397 |
E.coli, 541-15, replicate1 |
| GSM8133398 |
E.coli, 541-15, replicate2 |
| GSM8133399 |
E.coli, HM337, replicate1 |
| GSM8133400 |
E.coli, HM337, replicate2 |
| GSM8133401 |
E.coli, HM339, replicate1 |
| GSM8133402 |
E.coli, HM339, replicate2 |
| GSM8133403 |
E.coli, HM340, replicate1 |
| GSM8133404 |
E.coli, HM340, replicate2 |
| GSM8133405 |
E.coli, HM341, replicate1 |
| GSM8133406 |
E.coli, HM341, replicate2 |
| GSM8133407 |
E.coli, HM342, replicate1 |
| GSM8133408 |
E.coli, HM342, replicate2 |
| GSM8133409 |
E.coli, HM343, replicate1 |
| GSM8133410 |
E.coli, HM343, replicate2 |
| GSM8133411 |
E.coli, HM344, replicate1 |
| GSM8133412 |
E.coli, HM344, replicate2 |
| GSM8133413 |
E.coli, HM345, replicate1 |
| GSM8133414 |
E.coli, HM345, replicate2 |
| GSM8133415 |
E.coli, HM346, replicate1 |
| GSM8133416 |
E.coli, HM346, replicate2 |
| GSM8133417 |
E.coli, HM347, replicate1 |
| GSM8133418 |
E.coli, HM347, replicate2 |
| GSM8133419 |
E.coli, HM356, replicate1 |
| GSM8133420 |
E.coli, HM356, replicate2 |
| GSM8133421 |
E.coli, HM365, replicate1 |
| GSM8133422 |
E.coli, HM365, replicate2 |
| GSM8133423 |
E.coli, HM366, replicate1 |
| GSM8133424 |
E.coli, HM366, replicate2 |
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| Relations |
| BioProject |
PRJNA1085188 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261061_Core_gene_count.txt.gz |
221.1 Kb |
(ftp)(http) |
TXT |
| GSE261061_all_gene_count.txt.gz |
311.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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