{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334132/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Bos taurus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334132"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TLR4 governs strain-specific transcriptional responses of bovine mammary epithelial cells challenged by Staphylococcus aureus and its small colony variant","description":"Staphylococcus aureus small colony variants (SCVs) are metabolically adapted, slow-growing subpopulations responsible for chronic, recurrent bovine mastitis through enhanced intracellular persistence and immune evasion. The role of Toll-like receptor 4 (TLR4) in regulating bovine mammary epithelial transcriptional responses to S. aureus SCV challenge remains poorly understood. Using CRISPR-Cas9-generated TLR4-knockout (TLR4-KO) MAC-T cells combined with RNA sequencing, global transcriptional responses of wild-type (WT) and TLR4-KO MAC-T cells infected with S. aureus SCV Heba3231 and its isogenic parental strain (PS) were compared. The WT cells mounted highly divergent S. aureus strain-specific responses, with only 0.5% overlap in differentially expressed genes between PS and SCV conditions. The PS infection induced apoptotic and HIF-1 signalling pathways, whereas SCV infection promoted lipid metabolic reprogramming, accompanied by suppression of epithelial barrier integrity genes. TLR4 disruption dramatically amplified transcriptional dysregulation, with a 192-fold increase for the PS (1,921 DEGs) and a 6.6-fold increase for SCV (2,279 DEGs) relative to WT infected controls. This revealed a large core set of TLR4-regulated genes with approximately 57% shared across S. aureus strains that govern innate immunity, structural homeostasis, and apoptotic coordination. WFDC2, ITGB3, SH3BGRL, and HKDC1 emerged as novel TLR4-dependent candidate genes. Collectively, these findings identify TLR4 as a key determinant of strain-specific transcriptional discrimination and epithelial homeostasis during S. aureus infection, with particular relevance to SCV-mediated persistence in bovine mastitis.","dates":{"publication":"2026/06/08"},"accession":"GSE334132","cross_references":{"GSM":["GSM9781691","GSM9781692","GSM9781690","GSM9781695","GSM9781696","GSM9781693","GSM9781694","GSM9781699","GSM9781688","GSM9781689","GSM9781700","GSM9781697","GSM9781698","GSM9781701","GSM9781702"],"GPL":["35707"],"GSE":["334132"],"taxon":["Bos taurus"]}}