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Immunol."],"abstract":"<jats:p>\n                    Although sepsis is a leading cause of global mortality, the lack of reliable biomarkers hinders early risk stratification. Such biomarkers would facilitate timely and precise therapeutic interventions. Using a murine model of\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ) sepsis, we performed transcriptomic analysis and identified numerous genes that distinguished survivors from fatal cases. The top 16 candidate genes were further evaluated in patients with severe invasive bacterial infections. Among these,\n                    <jats:italic>complement receptor 2<\/jats:italic>\n                    (\n                    <jats:italic>CR2<\/jats:italic>\n                    ) was significantly downregulated in deceased patients compared with survivors and healthy controls. The extent of\n                    <jats:italic>CR2<\/jats:italic>\n                    downregulation was dependent on the administered dose of\n                    <jats:italic>S. aureus.<\/jats:italic>\n                    Time-course experiments conducted in infected mice showed progressive B-cell depletion and\n                    <jats:italic>CR2<\/jats:italic>\n                    downregulation, correlating with disease severity. Importantly,\n                    <jats:italic>CR2<\/jats:italic>\n                    downregulation was independent of complement factor 3, TLR2, and tumor necrosis (TNF)-\u03b1, but was reversed in infections with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    strains that lacked sortase A and B, and restored by antibiotic treatment of the infected mice. Loss of\n                    <jats:italic>CR2<\/jats:italic>\n                    expression may reflect B-cell activation followed by differentiation into plasmablasts and redistribution to secondary lymphoid organs. The present study suggests that\n                    <jats:italic>CR2<\/jats:italic>\n                    downregulation is associated with severe infection and mortality in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    sepsis and may represent a candidate biomarker of host immune dysregulation that warrants further validation in larger clinical cohorts.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1724049","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:19:19Z","timestamp":1783570759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement receptor 2 downregulation is associated with mortality in Staphylococcus aureus sepsis in both mice and humans"],"prefix":"10.3389","volume":"17","author":[{"given":"Pradeep Kumar","family":"Kopparapu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and 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Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Arif","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg","place":["Gothenburg, Sweden"]},{"name":"Science for Life Laboratory, University of Gothenburg","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Pekna","sequence":"additional","affiliation":[{"name":"Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Ljungstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Skaraborg Hospital","place":["Sk\u00f6vde, 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