{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:14Z","timestamp":1788419774861,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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-associated immune dysfunction varies across patients, compartments, and sampling windows. Dendritic cells (DCs) offer a useful\u2014but neither exclusive nor primary\u2014lens because they connect innate sensing with antigen presentation, cytokine instruction, and adaptive immunity. Human studies show reduced circulating DC abundance, altered phenotype, checkpoint context, and impaired ex vivo responsiveness, whereas experimental studies demonstrate splenic DC loss, disturbed bone-marrow generation, impaired anigen-specific T-cell priming, and tissue-specific pDC vulnerability or rescue. These observations support four distinct, potentially coexisting contributions: depletion, dysfunction of residual cells, redistribution, and impaired replacement. A low blood count cannot distinguish among them. Across mechanisms, evidence for developmental supply, survival and cell death, trafficking, antigen presentation, cytokine output, regulatory-like programming, checkpoint signaling, and organelle or metabolic stress varies substantially in identity confidence, model, functional validation, and causal support. Accordingly, human blood evidence is not treated as equivalent to murine marrow, spleen, or lung perturbation, and transcriptomic APC\/DC-like states are not equated with demonstrated cellular function. The mouse mregDC-like program remains a Class 4 exploratory regulatory-like state with substantial within-study support but no validated human sepsis homolog. Apparent conflicts\u2014including early inflammatory amplification versus persistent immune suppression, and IL-3-associated inflammation versus late pDC-dependent antiviral rescue\u2014are interpreted as context-, time-, and compartment-dependent rather than forced into a universal sequence. DC-informed monitoring should complement established broader approaches such as monocyte HLA-DR and transcriptomic immune subgrouping, using a transparent ten-domain appraisal of identity and evidence. No DC-only endotype, treatment trigger, bedside biomarker, or DC-directed therapy is validated. This synthesis defines testable, timing-aware, and safety-bounded research hypotheses while keeping clinical claims proportional to the evidence.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1934483","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:41:44Z","timestamp":1788417704000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dendritic-cell depletion and dysfunction in sepsis: a compartment- and evidence-aware synthesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoting","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Outpatient Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]},{"name":"Department of Emergency, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]},{"name":"NHC Key Laboratory of Chronobiology, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat Rev Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300171","article-title":"The calm after the storm: Implications of sepsis immunoparalysis on host immunity","volume":"211","author":"Silva","year":"2023","journal-title":"J Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0752-4","article-title":"An immune-cell signature of bacterial sepsis","volume":"26","author":"Reyes","year":"2020","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1430972","article-title":"Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis","volume":"15","author":"Pappa","year":"2024","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13054-025-05319-5","article-title":"An international observational study validating gene-expression sepsis immune subgroups","volume":"29","author":"Antcliffe","year":"2025","journal-title":"Crit Care"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1715812","article-title":"Immune signatures of sepsis from mild infection to critical illness - 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