{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T04:03:10Z","timestamp":1793592190886,"version":"4.5.0"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"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:p>Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the body\u2019s response to infection. It is characterized by a high incidence, high mortality rate, and high medical burden, and is a major global health threat. Although updated treatment guidelines have reduced the mortality rate during the acute phase, survivors still face a high long-term risk of recurrent infection and death. Recent studies have shown that the long-term high mortality rate of sepsis is closely related to the immunosuppression it induces. Sepsis-induced immunosuppression originates from the disruption of immune homeostasis, characterized by excessive release of anti-inflammatory cytokines, increased apoptosis of immune cells (especially lymphocytes), T cell exhaustion, and expansion of immune regulatory cells (Tregs, MDSCs). Reduced expression of human leukocyte antigen-DR (HLA-DR) and upregulated expression of immune checkpoint molecules (PD-1, CTLA-4, TIM-3, etc.) further exacerbate immunosuppression. This article systematically reviews the immune imbalance state and related mechanisms of patients with sepsis, and summarizes new immunotherapy strategies such as immune stimulatory factors (GM-CSF, IL-7, IL-15), immune checkpoint inhibitors (anti-PD-1\/PD-L1, anti-CTLA-4, anti-TIM-3), and emerging therapies (mesenchymal stem cells, calprotectin inhibitors, TREM-1 inhibitors). The aim is to enhance clinicians\u2019 understanding of sepsis-induced immunosuppression, facilitate early intervention, and reduce the incidence and mortality of long-term complications.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1643194","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T04:14:51Z","timestamp":1761279291000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The immunosuppressive mechanisms induced by sepsis and the corresponding treatment 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