Omics · study · 2026
Host response to bacteria induces a shift towards the enteroendocrine cell lineage in the murine enteroid model
Listed in NCBI GEO
The host response to commensal and pathogenic bacteria has been extensively characterized using human cancer cell line models, but remains poorly defined in primary intestinal cellular systems.
Description
Recent evidence has demonstrated that mice lacking the Nod-like receptor (NLR) protein NLRC4 are susceptible to S. flexneri infection and thus represent a new model to study the mechanistic aspects of S. flexneri -host interaction.
Using ileal organoids from wild type (WT) and Nlrc4-/- mice, we first confirmed that NLRC4 was required for the restriction of intracellular S. flexneri growth. Surprisingly, NLRC4 further mediated the detection of bacteria-free S. flexneri supernatants, suggesting that ileal organoids sample proteins from the type three secretion system (T3SS) to mediate a preemptive pyroptotic response to pathogens independently from invasion.
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Moreover, both invasive and non-invasive S. flexneri were found within Nlrc4-/- ileal organoids, suggesting that murine intestinal epithelial cells (IECs) may be capable of bacterial uptake. Transcriptional analysis further revealed that S. flexneri infection in Nlrc4-/- organoids resulted in the downregulation of inflammatory signaling, associated with an enrichment for markers of the enteroendocrine cell lineage (EEC).
This finding was recapitulated in organoids in contact with a non-pathogenic strain of S. flexneri, suggesting that EEC expansion depended on either bacterial contact or pickup. Together, our results reveal unexpected characteristics of host-bacterial interaction in primary murine IECs, which may shape the response to the microbiota and enteric pathogens at the intestinal mucosal surface
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305881 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305881 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1308115 ncbi.nlm.nih.gov/bioproject/PRJNA1308115 ↗
project · from NCBI GEO
- PubMed 41871150 pubmed.ncbi.nlm.nih.gov/41871150 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE305881 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |