{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306508/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306508"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Multimodal induction of hyperinflammation by IL-18 includes virus-specific NK immunodeficiency [NKILC1_RNAseq]","description":"Hemophagocytic Lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with multiple contributors and often an infectious trigger. The Macrophage Activation Syndrome (MAS) subtype is linked to marked IL-18 excess, cytotoxic T-lymphocyte (CTL) activation, and natural killer (NK) cell abnormalities. We asked how excess IL-18 shapes NK and CTL responses to viral challenge. Mice with chronic IL-18 overproduction (Il18tg), showed NK-cytopenia and baseline CTL activation resembling MAS-susceptible patients. NK transcriptomes indicated transcription/division with few changes in canonical NK programs. Infection of Il18tg mice with lymphocytic-choriomeningitis virus resulted in HLH/MAS but intact viral control. Early after NK-dependent mousepox infection, Il18tg NKs failed to appropriately activate but their CTLs became hyperactivated, and mousepox control remained intact. However, mousepox-infected Il18tg mice then developed hepatosplenic necrosis and other signs of HLH/MAS; and their poor viral control paralleled their failed expansion of mousepox-specific CTLs. Il18bpKO mice, despite more normal resting lymphocytes, succumbed similarly to viremic HLH/MAS. Transfer of pre-activated NKs into Il18tg mice restored their virus-specific CTL response and rescued survival. Thus, excess IL-18 contributes to HLH/MAS via disparate effects on CTL and NK cells, demonstrating a novel, context-specific NK immunodeficiency and highlighting how subtle host-pathogen interactions can affect the mechanisms and treatment rationale of life-threatening HLH/MAS.","dates":{"publication":"2026/08/25"},"accession":"GSE306508","cross_references":{"GSM":["GSM9202369","GSM9202367","GSM9202378","GSM9202368","GSM9202379","GSM9202372","GSM9202362","GSM9202373","GSM9202370","GSM9202381","GSM9202371","GSM9202365","GSM9202376","GSM9202377","GSM9202366","GSM9202374","GSM9202363","GSM9202375","GSM9202364","GSM9202380"],"GPL":["19057"],"GSE":["306508"],"taxon":["Mus musculus"]}}