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Although early clinical efforts were focused on increasing the survival of patients through the first phase, studies are now shifting attention to the long-term effects of sepsis on immune fitness in survivors. In particular, the most pertinent task is deciphering how the immune system becomes suppressed, leading to increased incidence of secondary infections. In this review, we introduce the contribution of numerical changes and functional reprogramming within innate (NK cells, dendritic cells) and adaptive (T cells, B cells) immune cells on the chronic immune dysregulation in the septic murine and human host. We briefly discuss how prior immunological experience in murine models impacts sepsis severity, immune dysfunction, and clinical relevance. Finally, we dive into how comorbidities, specifically autoimmunity and cancer, can influence host susceptibility to sepsis and the associated immune dysfunction.<\/jats:p>","DOI":"10.4049\/jimmunol.2300171","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T21:07:34Z","timestamp":1692652054000},"page":"711-719","source":"Crossref","is-referenced-by-count":55,"title":["The Calm after the Storm: Implications of Sepsis Immunoparalysis on Host Immunity"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2733-1999","authenticated-orcid":false,"given":"Elvia E","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-3553","authenticated-orcid":false,"given":"Cara","family":"Skon-Hegg","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2439","authenticated-orcid":false,"given":"Vladimir P","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-9859","authenticated-orcid":false,"given":"Thomas S","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Minneapolis VA Health Care System , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"2025020501013895200_r1","doi-asserted-by":"crossref","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":"2025020501013895200_r2","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1001\/jama.2017.13836","article-title":"Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009\u20132014","volume":"318","author":"Rhee","year":"2017","journal-title":"JAMA"},{"key":"2025020501013895200_r3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"2025020501013895200_r4","volume-title":"Healthcare Cost and Utilization Project (HCUP) Statistical Briefs","author":"Liang","year":"2020"},{"key":"2025020501013895200_r5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/01.CCM.0000194725.48928.3A","article-title":"Sepsis in European intensive care units: results of the SOAP study","volume":"34","author":"Vincent","year":"2006","journal-title":"Crit. 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