{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327545/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327545"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages","description":"Nearly 20% of SARS-CoV-2 infections result in ICU admission, often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion. The SARS-CoV-2 nucleocapsid (N) protein is a known immune antagonist, but its role in macrophage-driven cytokine storms is unclear. We demonstrate that N functions in a stimulus-specific manner, specifically amplifying extracellular and dampening intracellular RNA sensing. Moreover, we show that this is a conserved feature of pathogenic betacoronaviruses through distinct mechanisms. Our interaction networks with SARS-CoV-2 variant N proteins suggest the Delta variant N drives inflammation through interactions with several proteins, most notably, cGAS. Profiling of secreted cytokines revealed that the N proteins disrupt the secretome in a variant-specific manner. Most notably, we found that supernatants from the Delta variant N-expressing macrophages dramatically disrupt heart endothelial barriers, implicating N in COVID-19-associated cardiac complications. Our findings highlight N-mediated immune imbalance as a driver of severe COVID-19 and identify N as a promising therapeutic target to mitigate hyperinflammation.","dates":{"publication":"2026/06/25"},"accession":"GSE327545","cross_references":{"GSM":["GSM9661381","GSM9661370","GSM9661380","GSM9661372","GSM9661382","GSM9661371","GSM9661374","GSM9661373","GSM9661376","GSM9661375","GSM9661378","GSM9661367","GSM9661377","GSM9661369","GSM9661379","GSM9661368"],"GPL":["11154"],"GSE":["327545"],"taxon":["Homo sapiens"]}}