Omics · study · 2026
RANKL inhibits macrophage pro-inflammatory Toll-like receptor 2 and 4 signaling and impairs killing of intracellular bacteria
Listed in NCBI GEO
Monocyte-macrophage lineage cells, crucial components of the innate immune system, can uniquely form bone-resorbing osteoclasts upon exposure to the cytokine receptor activator of NF-κB ligand (RANKL) in the bone microenvironment.
Description
Recent studies have also begun to uncover extensive extraskeletal roles of RANKL. However, how monocyte-macrophage lineage cells respond to RANKL outside of the bone, and the impact that this signaling pathway exerts on the host immune response, is not fully understood.
In this study, we sought to define how RANKL exposure shapes the macrophage inflammatory response to pathogens by using the model intracellular bacterium Salmonella enterica serovar Typhimurium (STm), which co-opts macrophages to cause life-threatening infections. We found that exposing both mouse and human macrophages to sub-osteoclastogenic levels of RANKL increased intracellular STm burdens and decreased pro-inflammatory cytokine production.
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RNA sequencing revealed downregulation of pattern recognition receptor (PRR) signaling pathways in RANKL-treated macrophages during the early stages of infection. Therefore, we hypothesized that RANKL impairs PRR-dependent signaling pathways that are important for pro-inflammatory cytokine production. We discovered that RANKL-treated macrophages exhibit reduced NF-κB and IRF3 activation, specifically in response to Toll-like receptor (TLR) 2 and TLR4 stimulation.
We determined that prior RANKL exposure decreases abundance of the TLR2 and TLR4 adaptor proteins TRAM and TIRAP. Together, these data suggest that RANKL exposure negatively impacts the macrophage TLR-mediated inflammatory response to bacteria.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325337 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325337 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1439724 ncbi.nlm.nih.gov/bioproject/PRJNA1439724 ↗
project · from NCBI GEO
- PubMed 42177796 pubmed.ncbi.nlm.nih.gov/42177796 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE325337 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |