{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE344nnn/GSE344459/"]},"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=GSE344459"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Optineurin-deficiency Collapses the Host Endolysosomal Network and Impairs Xenophagy to Accelerate Mycobacterium tuberculosis Growth","description":"Selective autophagy is a host defense mechanism against Mycobacterium tuberculosis (Mtb) that restricts bacterial growth by targeting ubiquitin-coated bacilli for lysosomal degradation via autophagy receptors. Optineurin is a selective autophagy receptor that targets pathogens and modulates immune signaling, yet its precise structural mechanism during Mtb infection remains poorly defined. Here, we show that while Optineurin-deficiency spares the global host transcriptomic response to infection, it collapses the host endolysosomal network, decreasing LAMP1⁺ and LysoTracker⁺ reserves by half. Multi-dose bafilomycin A1 flux assays demonstrated that this structural depletion selectively blocks the dynamic, directional trafficking and functional delivery of autophagosomes to the pathogen, significantly reducing Mtb-DQ-BSA colocalization. Genetic complementation restored bacterial restriction in a manner dependent on three phosphosites (Ser187, Ser530, and the uncharacterized Ser556). In the context of reduced autophagic containment and increased Mtb replication, Optineurin-deficiency accelerated necrotic-like host cell death. In vivo, Optineurin-deficiency enhanced bacterial replication and impaired the Type I interferon response during acute Mtb infection but did not affect long-term survival. Together, these findings identify Optineurin as a critical regulator of autophagic flux, host cell death, and Type I interferon responses that limit early Mtb pathogenesis.","dates":{"publication":"2026/08/25"},"accession":"GSE344459","cross_references":{"GSM":["GSM9979302","GSM9979303","GSM9979300","GSM9979301","GSM9979306","GSM9979304","GSM9979305","GSM9979295","GSM9979298","GSM9979299","GSM9979296","GSM9979297"],"GPL":["34290"],"GSE":["344459"],"taxon":["Mus musculus"]}}