{"doi":"10.3389/fimmu.2022.865503","title":"Antibody-Mediated LILRB2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells to Kill Mycobacterium tuberculosis","abstract":"Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade of SHP1/2 phosphatase increased proinflammatory cytokine responses and phosphorylation of ERK1/2, p38 MAPK, and NF-kB in Mtb-infected MDSCs. LILRB2 antagonism also upregulated anti-mycobacterial iNOS gene expression and an increase in both nitric oxide and reactive oxygen species synthesis. Because genes associated with the anti-mycobacterial function of M1-MФs were enhanced in MDSCs following mab treatment, we propose that LILRB2 antagonism reprograms MDSCs from an immunosuppressive state towards a pro-inflammatory phenotype that kills Mtb. LILRB2 is therefore a novel therapeutic target for eradicating Mtb in MDSCs.","journal":"Frontiers in Immunology","year":2022,"id":270894,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":361039,"name":"Arshad Khan","orcid":"0000-0003-3655-2854","position":1,"is_corresponding":false},{"id":676907,"name":"Yitian Xu","orcid":"0000-0002-0558-3749","position":2,"is_corresponding":false},{"id":459648,"name":"Sunny Mai","orcid":"0000-0002-6782-7331","position":3,"is_corresponding":false},{"id":676906,"name":"Licheng Zhang","orcid":"0000-0002-0632-014X","position":4,"is_corresponding":false},{"id":568884,"name":"Abhishek Mishra","orcid":"0000-0003-2077-0937","position":5,"is_corresponding":false},{"id":297929,"name":"Blanca I. Restrepo","orcid":"0000-0002-3743-9098","position":6,"is_corresponding":false},{"id":459649,"name":"Ping‐Ying Pan","orcid":"0000-0002-2971-4221","position":7,"is_corresponding":false},{"id":315005,"name":"Shu‐Hsia Chen","orcid":"0000-0002-9168-5775","position":8,"is_corresponding":false},{"id":857902,"name":"Chinnaswamy Jagannath","orcid":"0000-0002-3014-2857","position":9,"is_corresponding":false},{"id":361040,"name":"Vipul K. Singh","orcid":"0000-0002-7146-7279","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:27:31.019242Z","pmid":"35757769","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":[]}