{"doi":"10.4049/jimmunol.2300107","title":"Impact of <i>Mycobacterium tuberculosis</i> Glycolipids on the CD4+ T Cell–Macrophage Immunological Synapse","abstract":"Mycobacterium tuberculosis cell-wall glycolipids such as mannosylated lipoarabinomannan (ManLAM) can inhibit murine CD4+ T cells by blocking TCR signaling. This results in suppression of IL-2 production, reduced T cell proliferation, and induction of CD4+ T cell anergy. This study extended these findings to the interaction between primary human CD4+ T cells and macrophages infected by mycobacteria. Exposure of human CD4+ T cells to ManLAM before activation resulted in loss of polyfunctionality, as measured by IL-2, IFN-γ, and TNF-α expression, and reduced CD25 expression. This was not associated with upregulation of inhibitory receptors CTLA-4, PD-1, TIM-3, and Lag-3. By confocal microscopy and imaging flow cytometry, ManLAM exposure reduced conjugate formation between macrophages and CD4+ T cells. ManLAM colocalized to the immunological synapse (IS) and reduced translocation of lymphocyte-specific protein tyrosine kinase (LCK) to the IS. When CD4+ T cells and Mycobacterium bovis BCG-infected monocytes were cocultured, ManLAM colocalized to CD4+ T cells, which formed fewer conjugates with infected monocytes. These results demonstrate that mycobacterial cell-wall glycolipids such as ManLAM can traffic from infected macrophages to disrupt productive IS formation and inhibit CD4+ T cell activation, contributing to immune evasion by M. tuberculosis.","journal":"The Journal of Immunology","year":2023,"id":350075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1012457,"name":"Rachel Shaw","orcid":"0000-0002-0438-7666","position":1,"is_corresponding":false},{"id":315156,"name":"Qing Li","orcid":"0000-0002-4982-1024","position":2,"is_corresponding":false},{"id":1094001,"name":"Shane Fletcher","orcid":"0000-0003-3594-8638","position":3,"is_corresponding":false},{"id":317195,"name":"Jacqueline M. Achkar","orcid":"0000-0002-5227-7293","position":4,"is_corresponding":false},{"id":812453,"name":"Clifford V. Harding","orcid":"0000-0002-6333-162X","position":5,"is_corresponding":false},{"id":481552,"name":"Stephen M. Carpenter","orcid":"0000-0001-9879-327X","position":6,"is_corresponding":false},{"id":231891,"name":"W. Henry Boom","orcid":"0000-0001-5760-9595","position":7,"is_corresponding":false},{"id":512903,"name":"Ivan Mwebaza","orcid":"0000-0002-7521-3305","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:12:23.769679Z","pmid":"37695687","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}