{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:43:18Z","timestamp":1773265398435,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The Myeloid DAP12-associating lectin-1 (MDL-1) serves as a pivotal pattern recognition receptor crucial for recognizing various pathogenic microorganisms and orchestrating immune responses during infections. This study aimed to elucidate the role of MDL-1 in the pathogenesis of sepsis-associated acute lung injury (ALI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experiments were conducted using wild-type (WT) and MDL-1-deficient (MDL-1\n                      <jats:sup>-\/-<\/jats:sup>\n                      ) mice on a C57BL\/6 background. Sepsis was induced by cecal ligation and puncture (CLP) surgery, with sham-operated mice serving as controls. Lung tissues were harvested 24 hours post-CLP for histopathological evaluation using hematoxylin and eosin (H&amp;amp;E) staining. MDL-1 expression on monocytes\/macrophages was analyzed by flow cytometry. Cytokines of IFN-\u03b3, IL-6, and TNF-\u03b1 were measured via ELISA. Protein expression was assessed by western blot, and mRNA levels of key cytokines and chemokines in lung tissues were quantified using real-time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Survival analysis revealed that MDL-1 deficiency significantly exacerbated mortality in septic mice. In the CLP-induced sepsis model, the 7-day survival rate was 78.6%  in the WT-CLP group, whereas it was markedly reduced to 42.9%  in the MDL-1\n                      <jats:sup>-\/-<\/jats:sup>\n                      -CLP group, demonstrating a statistically significant difference between the groups (P &amp;lt; 0.01). Histopathological assessment further confirmed that lung tissue damage was more severe in MDL-1\n                      <jats:sup>-\/-<\/jats:sup>\n                      -CLP mice compared to their WT-CLP counterparts, as evidenced by a significantly higher composite injury score. MDL-1 expression was markedly upregulated on monocytes and macrophages (P &amp;lt; 0.01). Serum IL-6 and TNF-\u03b1 levels were significantly elevated, whereas IFN-\u03b3 was reduced (P &amp;lt; 0.01). mRNA expression of cytokines and chemokines was correspondingly altered (P &amp;lt; 0.01). Furthermore, protein levels of phospho-Syk (p-Syk) and cleaved caspase-3 in lung tissues were significantly increased (P &amp;lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings demonstrate that MDL-1 deficiency exacerbates lung inflammation in a CLP-induced murine sepsis model. These results underscore the essential immunomodulatory role of MDL-1 in mitigating excessive pulmonary inflammatory responses during sepsis.<\/jats:p>\n                    <jats:p>\n                      The Myeloid DAP12-associating lectin-1 (MDL-1) serves as a pivotal pattern\u00a0recognition receptor crucial for recognizing various pathogenic microorganisms and orchestrating immune responses during infections. In this study, we elucidate that MDL-1 exhibits predominant expression within the mononuclear phagocyte system and plays a significant role in modulating the severity of lung injury in sepsis. Notably, MDL-1-deficient (MDL-1\n                      <jats:sup>-\/-<\/jats:sup>\n                      ) mice subjected to cecal ligation and puncture (CLP) exhibited elevated levels of pro-inflammatory cytokines such as IL-6 and TNF-\u03b1, along with decreased production of IFN-\u03b3. Moreover, the expression levels of chemokines like IP-10, KC, MCP-1, and MIP-1 were markedly upregulated in septic MDL-1\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice. Concurrently, enhanced levels of Syk and cleaved caspase 3 were detected in the lung tissues of MDL-1\n                      <jats:sup>-\/--<\/jats:sup>\n                      CLP animals, underscoring an augmented inflammatory response. Collectively, our findings indicate that MDL-1 deficiency correlates with the exacerbation of lung inflammation in a murine model of CLP-induced sepsis, highlighting the critical immunomodulatory role of MDL-1 in safeguarding against excessive pulmonary inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1709000","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:24Z","timestamp":1773207444000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The protective role of MDL-1 in sepsis-induced lung injury: insights from a murine CLP model"],"prefix":"10.3389","volume":"17","author":[{"given":"Baoji","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center","place":["Shanghai, China"]},{"name":"School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunpeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chinese People\u2019s Liberation Army 92493 Hospital","place":["Huludao, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daoqin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengzhi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulong","family":"Bo","sequence":"additional","affiliation":[{"name":"Faculty of Anesthesiology, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Pudong Gongli Hospital, Shanghai University of 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