{"database":"GEO","file_versions":[],"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=GSE331083"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Metabolic–Epigenetic Rewiring of CCR5 hi Monocytes Sustains Long-Term Trained Immunity Against Lethal Sepsis [bulk RNA-Seq]","description":"Trained immunity enhances innate host defense by endowing monocytes with memory-like properties, yet the underlying integrated metabolic and epigenetic mechanisms remain elusive. Here, we demonstrate that co-immunization with Bacillus Calmette–Guérin (BCG) and bacterial lipoprotein (BLP) induces a durable form of trained immunity that provides robust, long-term protection against polymicrobial sepsis from early life into adulthood. Single-cell RNA sequencing revealed that this effect is mediated by an expansion of CCR5hi memory-like monocytes with enhanced antimicrobial capacity. Mechanistically, BCG+BLP vaccination activated the AKT–mTOR–HIF-1α axis, driving glycolytic reprogramming and subsequent lactate accumulation. We found that elevated lactate then promoted KAT2B-dependent histone H3K18 lactylation, an epigenetic mark directly facilitating the transcription of phagocytic and inflammatory genes. Critically, CCR5hi monocytes isolated from vaccinated human cord blood recapitulated these lactate-driven lactylation and trained immunity features. Together, our findings define a novel lactate–KAT2B–H3K18la epigenetic axis that orchestrates the long-term reprogramming of CCR5hi monocytes, highlighting CCR5hi monocytes as a promising therapeutic target for modulating innate immunity against lethal sepsis","dates":{"publication":"2026/05/20"},"accession":"GSE331083","cross_references":{"GSM":["GSM9738693","GSM9738692","GSM9738691","GSM9738690","GSM9738689","GSM9738688"],"GPL":["24247"],"GSE":["331083"],"taxon":["Mus musculus"]}}