{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:27:30Z","timestamp":1789237650955,"version":"build-2803163510"},"reference-count":120,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222038"],"award-info":[{"award-number":["82222038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970259"],"award-info":[{"award-number":["81970259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502606"],"award-info":[{"award-number":["82502606"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Outstanding Youth in National Defense Science and Technology","award":["2023-JCJQ-ZQ-001"],"award-info":[{"award-number":["2023-JCJQ-ZQ-001"]}]},{"name":"Outstanding Young Talents of National Defense Biotechnology","award":["01-SWKJYCJJ06"],"award-info":[{"award-number":["01-SWKJYCJJ06"]}]},{"name":"Chongqing Outstanding Youth Fund","award":["CSTB2022NSCQ-JQX0017"],"award-info":[{"award-number":["CSTB2022NSCQ-JQX0017"]}]},{"name":"Military Clinical Key Specialty Construction Project"},{"name":"Chongqing Municipal Postdoctoral Research Project Special Funding Program","award":["2024CQBSHTB2010"],"award-info":[{"award-number":["2024CQBSHTB2010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Sepsis remains a leading cause of global mortality and is characterized by a dysregulated host immune response to infection. Early deaths often result from hyperinflammation and organ dysfunction, whereas late-stage mortality is increasingly attributed to sepsis-induced immunosuppression, leading to secondary infections and viral reactivation. Challenges persist in the identification and management of sepsis-induced immunosuppression, including the lack of standardized immune monitoring methods, the absence of reliable immune biomarkers to guide therapy, and the limited success of immunomodulatory therapies in clinical trials. This review comprehensively summarizes the pathophysiology of sepsis-induced immunosuppression, encompassing immune cell apoptosis and exhaustion, the expansion and activation of immunomodulatory cells, metabolic reprogramming, epigenetic alterations, and iatrogenic factors. We also discuss current diagnostic challenges and explore emerging immunomodulatory strategies, such as cytokine therapies, immune checkpoint inhibitors, and metabolic modulators, as potential approaches to restore immune function. Finally, we highlight the importance of immune phenotyping and individualized precision medicine in the future management of sepsis, and integrating multidisciplinary approaches from mechanistic research to targeted therapies holds promise for improving patient outcomes.<\/jats:p>","DOI":"10.3390\/pathogens15020159","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:48:08Z","timestamp":1770025688000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bench-to-Bedside Insights into the Challenges of Immunosuppression in Sepsis"],"prefix":"10.3390","volume":"15","author":[{"given":"Shaowen","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"},{"name":"Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-8137","authenticated-orcid":false,"given":"Siyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"},{"name":"Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huacai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Unit 94654 of the Chinese People\u2019s Liberation Army, Nanjing 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, National Clinical Research Centre for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9640-9083","authenticated-orcid":false,"given":"Ling","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1056\/NEJMra2403213","article-title":"Sepsis and Septic Shock","volume":"391","author":"Meyer","year":"2024","journal-title":"N. 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