{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336443/"]},"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=GSE336443"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Restricted MHCII trafficking in Mycobacterium tuberculosis-infected M2-like macrophages limits CD4+ T cell activation","description":"Recognition of infected macrophages by CD4+ T cells is essential to immune protection against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). However, not all infected macrophage subsets successfully elicit T cell activation. We recently discovered that M2-like macrophages fail to efficiently activate memory CD4+ T cells when infected with Mtb, yet successfully elicit T cell activation when loaded with peptides, g-irradiated bacteria, or Mtb whole cell lysate. Since the mechanisms underlying CD4+ T-cell evasion by infected M2 but not M1-like macrophages remain underexplored, we sought to determine the genes and pathways unique to Mtb infection of M2-like cells, including alveolar macrophages. RNA sequencing of macrophage subsets infected with virulent Mtb identified enrichment of IL-10 and type I IFN signaling pathway genes, including IL10RA and HERC5, respectively, in infected M2-like and human alveolar macrophages. However, genes involved in MHC II trafficking, such as AP1M2, were higher in infected M1-like macrophages. In complementary experiments using fluorescent microscopy and flow cytometry, we observed impaired trafficking of newly synthesized MHC II to the plasma membrane of Mtb-infected M2-like macrophages despite high total surface MHC II levels. Neutralization of IL-10 or knockdown of HERC5 restored MHC II trafficking to the cell surface among infected M2-like macrophages and significantly enhanced activation of memory CD4+ T cells in an MHC II-dependent manner. These findings identify coordinated IL-10 and type I IFN signaling as key mechanisms that restrict MHC II trafficking to the plasma membrane in Mtb-infected M2-like macrophages, thereby limiting antigen presentation and CD4+ T cell activation. We propose that host-directed therapies targeting these pathways in infected alveolar macrophages will facilitate T cell recognition for the prevention or treatment of active TB.","dates":{"publication":"2026/09/25"},"accession":"GSE336443","cross_references":{"GSM":["GSM9835381","GSM9835341","GSM9835342","GSM9835386","GSM9835383","GSM9835384","GSM9835422","GSM9835387","GSM9835420","GSM9835344","GSM9835349","GSM9835426","GSM9835425","GSM9835347","GSM9835429","GSM9835428","GSM9835393","GSM9835390","GSM9835391","GSM9835397","GSM9835353","GSM9835351","GSM9835395","GSM9835356","GSM9835433","GSM9835354","GSM9835432","GSM9835431","GSM9835399","GSM9835437","GSM9835435","GSM9835360","GSM9835440","GSM9835362","GSM9835400","GSM9835367","GSM9835322","GSM9835366","GSM9835327","GSM9835325","GSM9835402","GSM9835369","GSM9835409","GSM9835406","GSM9835329","GSM9835371","GSM9835331","GSM9835373","GSM9835334","GSM9835378","GSM9835379","GSM9835412","GSM9835376","GSM9835410","GSM9835339","GSM9835416","GSM9835336","GSM9835413"],"GPL":["24676"],"GSE":["336443"],"taxon":["Homo sapiens"],"PMID":["[42465483]"]}}