{"doi":"10.1126/scitranslmed.adp1349","title":"<i>Pseudomonas aeruginosa</i> infection induces intragraft lymphocytotoxicity that triggers lung transplant antibody-mediated rejection","abstract":"How pathogens inhibit transplant tolerance remains unclear. Here, we found that Pseudomonas aeruginosa infection, but not other common bacterial respiratory infections, increases antibody-mediated rejection (AMR) risk in recipients of lung transplants. To explore this relationship, we performed orthotopic lung transplants in mice, infected recipients with P. aeruginosa , and observed for the development of AMR. Intravital two-photon microscopy showed that P. aeruginosa rapidly invaded bronchial-associated lymphoid tissues, which resulted in acute lymphocytotoxicity, including the death of forkhead box P3 (Foxp3) + CD4 + T cells that are required to suppress AMR. P. aeruginosa –mediated AMR required expression of the type III secretion system (T3SS), which injects exotoxins into the cell cytoplasm. Through a combination of mutagenesis and epitope tagging experiments, we revealed that T3SS exotoxin T ADP ribosyl-transferase activity was sufficient for graft-resident Foxp3 + CD4 + T cell apoptosis, leading to myeloid differentiation primary response 88 (Myd88)–dependent generation of T-box expressed in T cells (T-bet)– and C-X-C motif chemokine receptor 3 (CXCR3)–positive germinal center and memory B cells with high donor antigen avidity. We also found that T-bet + and CXCR3 + B cells were elevated in biopsies from recipients of lung transplants who were diagnosed with AMR. In mice, CXCR3 deficiency restricted to B cells or CXCR3 blockade prevented AMR despite P. aeruginosa infection. Our work has identified a previously unrecognized role of bacterial virulence in lung allograft rejection and suggests potential strategies to prevent AMR for those at high risk of P. aeruginosa infection after transplant.","journal":"Science Translational Medicine","year":2025,"id":510951,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":868537,"name":"Dequan Zhou","orcid":"0009-0009-7288-9981","position":1,"is_corresponding":false},{"id":337924,"name":"Marlene Cano","orcid":"0000-0002-2368-9256","position":2,"is_corresponding":false},{"id":1368138,"name":"Zhiyi Liu","orcid":"0009-0008-9452-0547","position":3,"is_corresponding":false},{"id":363614,"name":"Davide Scozzi","orcid":"0000-0002-4049-1591","position":4,"is_corresponding":false},{"id":704699,"name":"Laneshia K. Tague","orcid":"0000-0002-6243-1901","position":5,"is_corresponding":false},{"id":273857,"name":"Derek E. Byers","orcid":"0000-0001-7371-9153","position":6,"is_corresponding":false},{"id":376146,"name":"Wenjun Li","orcid":"0000-0002-1923-5016","position":7,"is_corresponding":false},{"id":420228,"name":"Jothilingam Sivapackiam","orcid":"0000-0001-7979-1893","position":8,"is_corresponding":false},{"id":420230,"name":"Vijay Sharma","orcid":"0000-0002-4985-0044","position":9,"is_corresponding":false},{"id":267156,"name":"Alexander S. Krupnick","orcid":"0000-0002-1790-6197","position":10,"is_corresponding":false},{"id":384894,"name":"Dara W. Frank","orcid":"0000-0003-1853-3377","position":11,"is_corresponding":false},{"id":273856,"name":"Daniel Kreisel","orcid":"0000-0002-7711-8651","position":12,"is_corresponding":false},{"id":230294,"name":"Hrishikesh S. Kulkarni","orcid":"0000-0003-4830-5084","position":13,"is_corresponding":false},{"id":288869,"name":"Ramsey R. Hachem","orcid":"0000-0002-0708-1937","position":14,"is_corresponding":false},{"id":230331,"name":"Andrew E. Gelman","orcid":"0000-0002-0711-6343","position":15,"is_corresponding":false},{"id":497620,"name":"Fuyi Liao","orcid":"0000-0001-7733-084X","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:47:50.575618Z","pmid":"39908350","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":[]}