{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:54:12Z","timestamp":1791554052950,"version":"4.3.4"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL146266"],"award-info":[{"award-number":["R01HL146266"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Veterans Affairs","award":["I01 BX004441"],"award-info":[{"award-number":["I01 BX004441"]}],"id":[{"id":"https:\/\/ror.org\/05rsv9s98","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,8,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Pneumocystis jirovecii<\/jats:italic>\n                      pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV\/AIDS or undergoing immunosuppressive therapies for cancer or solid organ transplants. Severe PjP triggers excessive lung inflammation, resulting in lung function decline and consequential alveolar damage, potentially culminating in acute respiratory distress syndrome. Non-HIV patients face a 30%\u201360% mortality rate, emphasizing the need for a deeper understanding of inflammatory responses in PjP. Prior research emphasized macrophages in\n                      <jats:italic toggle=\"yes\">Pneumocystis<\/jats:italic>\n                      infections, neglecting neutrophils\u2019 role in tissue damage. Consequently, the overemphasis on macrophages led to an incomplete understanding of the role of neutrophils and inflammatory responses. In the current investigation, our RNAseq studies on a murine surrogate model of PjP revealed heightened activation of the NLRP3 inflammasome and NETosis cell death pathways in their lungs. Immunofluorescence staining confirmed neutrophil extracellular trap (NET) presence in the lungs of the\n                      <jats:italic toggle=\"yes\">P. murina<\/jats:italic>\n                      -infected mice, validating our findings. Moreover, isolated neutrophils exhibited NETosis when directly stimulated with\n                      <jats:italic toggle=\"yes\">P. murina<\/jats:italic>\n                      . Isolated NETs compromised\n                      <jats:italic toggle=\"yes\">P. murina<\/jats:italic>\n                      viability\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , highlighting the potential role of neutrophils in controlling fungal growth and promoting inflammation during\n                      <jats:italic toggle=\"yes\">P. murina<\/jats:italic>\n                      pneumonia through NLRP3 inflammasome assembly and NETosis. These pathways, essential for inflammation and pathogen elimination, bear the risk of uncontrolled activation leading to excessive tissue damage and persistent inflammation. This pioneering study is the first to identify the formation of NETs and inflammasomes during\n                      <jats:italic toggle=\"yes\">Pneumocystis<\/jats:italic>\n                      infection, paving the way for comprehensive investigations into treatments aimed at mitigating lung damage and augmenting survival rates for individuals with\n                      <jats:italic toggle=\"yes\">PjP<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Pneumocystis jirovecii<\/jats:italic>\n                        pneumonia (PjP) affects individuals with weakened immunity, such as HIV\/AIDS, cancer, and organ transplant patients. Severe PjP triggers lung inflammation, impairing function and potentially causing acute respiratory distress syndrome. Non-HIV individuals face a 30%\u201360% mortality rate, underscoring the need for deeper insight into PjP\u2019s inflammatory responses. Past research focused on macrophages in managing\n                        <jats:italic toggle=\"yes\">Pneumocystis<\/jats:italic>\n                        infection and its inflammation, while the role of neutrophils was generally overlooked. In contrast, our findings in\n                        <jats:italic toggle=\"yes\">P. murina<\/jats:italic>\n                        -infected mouse lungs showed neutrophil involvement during inflammation and increased expression of NLRP3 inflammasome and NETosis pathways. Detection of neutrophil extracellular traps further indicated their involvement in the inflammatory process. Although beneficial in combating infection, unregulated neutrophil activation poses a potential threat to lung tissues. Understanding the behavior of neutrophils in\n                        <jats:italic toggle=\"yes\">Pneumocystis<\/jats:italic>\n                        infections is crucial for controlling detrimental reactions and formulating treatments to reduce lung damage, ultimately improving the survival rates of individuals with PjP.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01409-24","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T06:19:01Z","timestamp":1719901141000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["<i>Pneumocystis murina<\/i>\n                    promotes inflammasome formation and NETosis during\n                    <i>Pneumocystis<\/i>\n                    pneumonia"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7461-0704","authenticated-orcid":true,"given":"Steven G.","family":"Sayson","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine","place":["Cincinnati, USA"]},{"name":"The Veterans Affairs Medical Center","place":["Cincinnati, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-439X","authenticated-orcid":false,"given":"Alan","family":"Ashbaugh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine","place":["Cincinnati, USA"]},{"name":"The Veterans Affairs Medical Center","place":["Cincinnati, 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