{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:54:40Z","timestamp":1785779680379,"version":"3.56.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007048","name":"Mayo Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Walter and Leonore Annenberg Foundation"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21-AI181542-01-02"],"award-info":[{"award-number":["R21-AI181542-01-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01-HL62150"],"award-info":[{"award-number":["R01-HL62150"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alveolar macrophages (AMs) are central to host defense against Pneumocystis, mediating organism clearance while also contributing to lung inflammation. EphA2, a transmembrane receptor that binds fungal \u03b2-glucans, has emerged as a regulator of host\u2013pathogen interactions, but its role in AM responses during Pneumocystis pneumonia (PCP) is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated AM inflammatory responses to Pneumocystis \u03b2-glucans in the presence and absence of EphA2. In vivo studies used a CD4-depleted mouse model of PCP comparing wild-type and EphA2-deficient (EphA2\u2212\/\u2212) mice. Lung cytokine responses and organism burden were assessed. Additionally, EphA2 signaling was pharmacologically inhibited using ALW-II-41-27 during trimethoprim-sulfamethoxazole treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EphA2 deficiency significantly reduced AM proinflammatory cytokine responses to Pneumocystis \u03b2-glucans. In CD4-depleted PCP mice, EphA2\u2212\/\u2212 animals demonstrated decreased lung inflammatory cytokines, but increased organism burden compared to controls. Pharmacologic inhibition of EphA2 during antimicrobial therapy significantly suppressed lung inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EphA2 signaling plays a critical role in AM-mediated host defense against Pneumocystis by promoting inflammatory responses necessary for organism control. However, this pathway also contributes to lung inflammation. Targeting EphA2 may represent a novel strategy to modulate inflammation during severe PCP while preserving antimicrobial defense.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag228","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:28:13Z","timestamp":1776770893000},"page":"154-163","source":"Crossref","is-referenced-by-count":1,"title":["The Tyrosine Kinase Receptor EphA2 in Alveolar Macrophages Provides a Protective Role in Host Defense Against\n                    <i>Pneumocystis<\/i>\n                    Pneumonia"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-3311","authenticated-orcid":false,"given":"Theodore J","family":"Kottom","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Thoracic Diseases Research Unit, Mayo Clinic College of Medicine , 221 First Street SW, Rochester, Minnesota 55905 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