{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:06:25Z","timestamp":1780556785140,"version":"3.54.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Chongqing Natural Science Foundation General Project","award":["CSTB2024NSCO-MSX0439"],"award-info":[{"award-number":["CSTB2024NSCO-MSX0439"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Burkholderia thailandensis (B. thailandensis) is an emerging pathogen. Although it has not yet caused large-scale outbreaks, severe infections can lead to sepsis. Currently, there are no effective treatment strategies available, highlighting the urgent need to develop novel therapies. Progranulin (PGRN) is a multifunctional protein with complex roles in regulating infectious processes. Our study investigated the role and mechanism of PGRN in host defense against lethal B. thailandensis infection. We found that PGRN expression was significantly upregulated during B. thailandensis infection. Compared with wild-type (WT) mice, PGRN knockout (PGRN\u2212\/\u2212) mice exhibited significantly higher mortality, increased bacterial burdens in tissues, and more severe liver injury. Further analysis revealed that the heightened susceptibility of PGRN\u2212\/\u2212 mice was closely associated with impaired phagocytic and bactericidal activities of macrophages. Mechanistically, RNA sequencing and Western blot analysis demonstrated that PGRN deficiency attenuated the activation of the JAK1-STAT3 signaling pathway in macrophages. Importantly, pharmacological activation of STAT3 rescued antimicrobial defects in PGRN\u2212\/\u2212 macrophages and significantly improved the survival rate of PGRN\u2212\/\u2212 mice infected with B. thailandensis. Collectively, our findings identify PGRN as a critical host defense factor that enhances macrophage antibacterial function via JAK1-STAT3 pathway, thereby protecting against lethal B. thailandensis sepsis. These results highlight the potential of PGRN as a promising therapeutic target for the treatment of B. thailandensis-induced sepsis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag069","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:39:52Z","timestamp":1780555192000},"source":"Crossref","is-referenced-by-count":0,"title":["PGRN promotes host defense against\n                    <i>B. thailandensis-<\/i>\n                    induced sepsis by augmenting macrophage antibacterial capacity via JAK1-STAT3 pathway"],"prefix":"10.1093","volume":"215","author":[{"given":"Kuiling","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Affiliated Dazu\u2019s Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renlin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Seventh People\u2019s Hospital of Chongqing, Central Hospital Affiliated to Chongqing University of Technology , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Affiliated Dazu\u2019s Hospital of Chongqing Medical University , Chongqing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026060402394943200_vkag069-B1","doi-asserted-by":"crossref","DOI":"10.1099\/jmm.0.001688","article-title":"Genomic features and virulence characteristics of a rare Burkholderia thailandensis strain causing human infection","volume":"72","author":"Li","year":"2023","journal-title":"J Med Microbiol"},{"key":"2026060402394943200_vkag069-B2","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.3201\/eid2411.180821","article-title":"Burkholderia thailandensis isolated from infected wound, Arkansas, USA","volume":"24","author":"Gee","year":"2018","journal-title":"Emerg Infect Dis"},{"key":"2026060402394943200_vkag069-B3","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.3201\/eid2308.170048","article-title":"Human infection with Burkholderia thailandensis, China, 2013","volume":"23","author":"Chang","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2026060402394943200_vkag069-B4","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1016\/j.radcr.2024.08.121","article-title":"Cardiac and mediastinum involvement in Burkholderia thailandensis infection: a case report and literature review","volume":"19","author":"Kaeorat","year":"2024","journal-title":"Radiol Case Rep"},{"key":"2026060402394943200_vkag069-B5","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3201\/eid3005.230743","article-title":"Burkholderia thailandensis isolated from infected wound, southwest China, 2022","volume":"30","author":"Li","year":"2024","journal-title":"Emerg Infect Dis"},{"key":"2026060402394943200_vkag069-B6","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.3389\/fmicb.2019.01483","article-title":"Molecular mechanisms of AhpC in resistance to oxidative stress in Burkholderia thailandensis","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Microbiol"},{"key":"2026060402394943200_vkag069-B7","doi-asserted-by":"crossref","first-page":"811343","DOI":"10.3389\/fmicb.2021.811343","article-title":"Characterization of a type VI secretion system vgrG2 gene in the pathogenicity of Burkholderia thailandensis BPM","volume":"12","author":"Li","year":"2021","journal-title":"Front Microbiol"},{"key":"2026060402394943200_vkag069-B8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fcimb.2017.00231","article-title":"Pkc-\u03b7-marcks signaling promotes intracellular survival of un-opsonized Burkholderia thailandensis","volume":"7","author":"Micheva-Viteva","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"2026060402394943200_vkag069-B9","doi-asserted-by":"crossref","first-page":"e0205421","DOI":"10.1128\/mBio.02054-21","article-title":"Guanylate-binding protein-dependent noncanonical inflammasome activation prevents 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