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Comprehensive mechanistic understanding of these phases is largely lacking. To address this gap, we leveraged a controlled, human in vivo model of lipopolysaccharide (LPS)-induced systemic inflammation encompassing both phases. Single-cell RNA sequencing during the acute hyperinflammatory phase identified an inflammatory <jats:italic>CD163<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>SLC39A8<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>CALR<\/jats:italic>\n            <jats:sup>+<\/jats:sup> monocyte-like subset (infMono) at 4\u2009h post-LPS administration. The late immunosuppressive phase was characterized by diminished expression of type I interferon (IFN)-responsive genes in monocytes, impaired myelopoiesis and a pronounced attenuation of the immune response on a secondary LPS challenge 1\u2009week after the first. The infMono gene program and impaired myelopoiesis were also detected in patient cohorts with bacterial sepsis and coronavirus disease. IFN\u03b2 treatment restored type-I IFN responses and proinflammatory cytokine production and induced monocyte maturation, suggesting a potential treatment option for immunosuppression.<\/jats:p>","DOI":"10.1038\/s41590-025-02136-4","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T09:02:03Z","timestamp":1744966923000},"page":"737-747","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Systemic inflammation impairs myelopoiesis and interferon type I responses in humans"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-4133","authenticated-orcid":false,"given":"Farid","family":"Keramati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guus P.","family":"Leijte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Bruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Grondman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7208-7999","authenticated-orcid":false,"given":"Ehsan","family":"Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-7964","authenticated-orcid":false,"given":"Cristian","family":"Ruiz-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wout","family":"Megchelenbrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke M.","family":"Peters van Ton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidde","family":"Heesakkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manita E.","family":"Bremmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7743-194X","authenticated-orcid":false,"given":"Erinke","family":"van Grinsven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiki","family":"Tesselaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"van Staveren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"van der Velden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Preijers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2777-2540","authenticated-orcid":false,"given":"Brigit","family":"te Pas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"van de Loop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-7350","authenticated-orcid":false,"given":"Jelle","family":"Gerretsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-6052","authenticated-orcid":false,"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0066-1576","authenticated-orcid":false,"given":"Hendrik G.","family":"Stunnenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1104-4303","authenticated-orcid":false,"given":"Peter","family":"Pickkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6537-6971","authenticated-orcid":false,"given":"Matthijs","family":"Kox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"2136_CR1","doi-asserted-by":"publisher","first-page":"S64","DOI":"10.1007\/s001340051121","volume":"26","author":"C Brun-Buisson","year":"2000","unstructured":"Brun-Buisson, C. 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