{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:33Z","timestamp":1792787613906,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["226817\/Z\/22\/Z"],"award-info":[{"award-number":["226817\/Z\/22\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["214321\/Z\/18\/Z"],"award-info":[{"award-number":["214321\/Z\/18\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["203135\/Z\/16\/Z"],"award-info":[{"award-number":["203135\/Z\/16\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["098316"],"award-info":[{"award-number":["098316"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MR\/R008922\/1"],"award-info":[{"award-number":["MR\/R008922\/1"]}]},{"name":"National Institute for Health and Care Research","award":["134342"],"award-info":[{"award-number":["134342"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute for Health and Care Research","award":["303140"],"award-info":[{"award-number":["303140"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIHR Imperial Biomedical Research Centre","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/01kmhx639","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation","award":["64787"],"award-info":[{"award-number":["64787"]}]},{"name":"US National Institutes of Health","award":["R01AI120033"],"award-info":[{"award-number":["R01AI120033"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"US National Institutes of Health","award":["R21AI182432"],"award-info":[{"award-number":["R21AI182432"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n                    pneumonia (PCP) remains a major cause of life-threatening respiratory failure in people with advanced HIV, yet the biological factors associated with mortality are incompletely understood. We performed integrated transcriptomic, proteomic, and metabolomic profiling of bronchoalveolar lavage fluid from 42 adults with HIV-associated PCP, relating molecular signatures to mortality. We found that fungal burden, measured by sputum immunofluorescence,\n                    <jats:italic>Pneumocystis<\/jats:italic>\n                    qPCR, and 1,3-\u03b2-D-glucan, did not differ between survivors and non-survivors or correlate with baseline gas exchange. Instead, non-survivors exhibited a bronchoalveolar immunometabolic failure signature characterised by marked depletion of immunoglobulins and complement, reduced pattern recognition receptors and fibroblast growth factor family proteins, and broad disruption of extracellular matrix organisation. Metabolomic profiling revealed enrichment of arginine-urea cycle and tricarboxylic acid pathways, with coordinated accumulation of arginine, citrulline, and TCA cycle intermediates consistent with nitrosative and mitochondrial stress. An integrated proteo-metabolomic score summarising this state was significantly higher in non-survivors and did not correlate with fungal burden or cytomegalovirus co-infection. In an immunodeficient precision-cut lung slice model, antigen-screened intravenous immunoglobulin restored macrophage-mediated\n                    <jats:italic>Pneumocystis<\/jats:italic>\n                    clearance, providing proof-of-concept for opsonic augmentation. Our findings indicate that mortality in HIV-PCP is defined by profound immunometabolic failure, highlighting humoral depletion and impaired alveolar repair as potential targets for host-directed adjunctive therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.206942","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:28Z","timestamp":1791302428000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analyses reveal key immunological and metabolic correlates of mortality in HIV-associated Pneumocystis pneumonia"],"prefix":"10.1172","author":[{"given":"Peter","family":"Rossi-Smith","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayanda Trevor","family":"Mnguni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Stellenbosch, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-2543","authenticated-orcid":true,"given":"Dora","family":"Pungan","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi R.","family":"Kumaran","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Ferris","sequence":"additional","affiliation":[{"name":"Agilent Measurement Suite, Department of Chemistry, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Skirlo","sequence":"additional","affiliation":[{"name":"Agilent Measurement Suite, Department of Chemistry, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N.","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelesh P.","family":"Govender","sequence":"additional","affiliation":[{"name":"Africa Unit, MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Blizard Institute, Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-6304","authenticated-orcid":true,"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel P.J.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,6]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/206942\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:30Z","timestamp":1791302430000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/206942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.206942"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.206942","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}