{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:56:07Z","timestamp":1791924967470,"version":"4.3.4"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI072571"],"award-info":[{"award-number":["AI072571"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["HL145997"],"award-info":[{"award-number":["HL145997"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["CA009161"],"award-info":[{"award-number":["CA009161"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["CA232666"],"award-info":[{"award-number":["CA232666"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI128949"],"award-info":[{"award-number":["AI128949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI128949"],"award-info":[{"award-number":["AI128949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI158808"],"award-info":[{"award-number":["AI158808"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EI1185\/1-1"],"award-info":[{"award-number":["EI1185\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Plasmacytoid dendritic cells (pDCs) mount powerful antiviral type I interferon (IFN-I) responses, yet only a fraction of pDCs produces high levels of IFN-I. Here we report that peripheral pDCs in naive mice comprise three subsets (termed A, B and C) that represent progressive differentiation stages. This heterogeneity was generated by tonic IFN-I signaling elicited in part by the cGAS\/STING and TLR9 DNA-sensing pathways. A small \u2018IFN-I-naive\u2019 subset (pDC-A) could give rise to other subsets; it was expanded in STING deficiency or after the IFN-I receptor blockade, but was abolished by exogenous IFN-I. In response to RNA viruses, pDC-A showed increased Bcl2-dependent survival and superior IFN-I responses, but was susceptible to virus infection. Conversely, the majority of pDCs comprised the \u2018IFN-I-primed\u2019 subsets (pDC-B\/C) that showed lower IFN-I responses and poor survival, but did not support virus replication. Thus, tonic IFN-I signaling decreases the cytokine-producing capacity and survival of pDCs but increases their virus resistance, facilitating optimal antiviral responses.<\/jats:p>","DOI":"10.1038\/s41590-025-02279-4","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T09:03:07Z","timestamp":1760432587000},"page":"1946-1961","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-8046","authenticated-orcid":false,"given":"Joseph N.","family":"Pucella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul A.","family":"Maqueda-Alfaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-6967","authenticated-orcid":false,"given":"Fernando","family":"Bandeira Sulczewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2256-6633","authenticated-orcid":false,"given":"Anna","family":"Eichinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-6632","authenticated-orcid":false,"given":"Eduardo","family":"Esteva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai C.","family":"Ra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annesa","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana A.","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon","family":"Stoeckius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Smibert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Khodadadi-Jamayran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4451-126X","authenticated-orcid":false,"given":"Igor","family":"Dolgalev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-9505","authenticated-orcid":false,"given":"Ellie","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stela","family":"Sota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-0661","authenticated-orcid":false,"given":"Ken","family":"Cadwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei B.","family":"Koralov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetna","family":"Soni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Stetson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-5976","authenticated-orcid":false,"given":"Stuart P.","family":"Weisberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-9183","authenticated-orcid":false,"given":"Donna L.","family":"Farber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-8862","authenticated-orcid":false,"given":"Juliana","family":"Idoyaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-7853","authenticated-orcid":false,"given":"Boris","family":"Reizis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"2279_CR1","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41564-019-0421-x","volume":"4","author":"EV Mesev","year":"2019","unstructured":"Mesev, E. V., LeDesma, R. A. & Ploss, A. Decoding type I and III interferon signalling during viral infection. Nat. Microbiol. 4, 914\u2013924 (2019).","journal-title":"Nat. Microbiol."},{"key":"2279_CR2","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","volume":"20","author":"M Motwani","year":"2019","unstructured":"Motwani, M., Pesiridis, S. & Fitzgerald, K. A. DNA sensing by the cGAS-STING pathway in health and disease. Nat. Rev. Genet. 20, 657\u2013674 (2019).","journal-title":"Nat. Rev. Genet."},{"key":"2279_CR3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1146\/annurev-immunol-090122-041105","volume":"42","author":"NM Adams","year":"2024","unstructured":"Adams, N. M., Das, A., Yun, T. J. & Reizis, B. Ontogeny and function of plasmacytoid dendritic cells. Annu. Rev. Immunol. 42, 347\u2013373 (2024).","journal-title":"Annu. Rev. Immunol."},{"key":"2279_CR4","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.immuni.2010.11.020","volume":"33","author":"M Swiecki","year":"2010","unstructured":"Swiecki, M., Gilfillan, S., Vermi, W., Wang, Y. & Colonna, M. Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8+ T cell accrual. Immunity 33, 955\u2013966 (2010).","journal-title":"Immunity"},{"key":"2279_CR5","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1182\/blood-2006-05-023770","volume":"109","author":"L Cervantes-Barragan","year":"2007","unstructured":"Cervantes-Barragan, L. et al. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood 109, 1131\u20131137 (2007).","journal-title":"Blood"},{"key":"2279_CR6","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1073\/pnas.1117359109","volume":"109","author":"L Cervantes-Barragan","year":"2012","unstructured":"Cervantes-Barragan, L. et al. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc. Natl Acad. Sci. USA 109, 3012\u20133017 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2279_CR7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cell.2008.09.016","volume":"135","author":"B Cisse","year":"2008","unstructured":"Cisse, B. et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135, 37\u201348 (2008).","journal-title":"Cell"},{"key":"2279_CR8","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/s41590-023-01454-9","volume":"24","author":"M Valente","year":"2023","unstructured":"Valente, M. et al. Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells. Nat. Immunol. 24, 714\u2013728 (2023).","journal-title":"Nat. Immunol."},{"key":"2279_CR9","doi-asserted-by":"publisher","first-page":"3736","DOI":"10.1016\/j.celrep.2019.11.042","volume":"29","author":"R Leylek","year":"2019","unstructured":"Leylek, R. et al. Integrated cross-species analysis identifies a conserved transitional dendritic cell population. Cell Rep. 29, 3736\u20133750 (2019).","journal-title":"Cell Rep."},{"key":"2279_CR10","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/s41590-023-01545-7","volume":"24","author":"FB Sulczewski","year":"2023","unstructured":"Sulczewski, F. B. et al. Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses. Nat. Immunol. 24, 1265\u20131280 (2023).","journal-title":"Nat. Immunol."},{"key":"2279_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add4132","volume":"8","author":"PF Rodrigues","year":"2023","unstructured":"Rodrigues, P. F. et al. pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells. Sci. Immunol. 8, eadd4132 (2023).","journal-title":"Sci. Immunol."},{"key":"2279_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106019","volume":"26","author":"F Brouiller","year":"2023","unstructured":"Brouiller, F. et al. Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells. iScience 26, 106019 (2023).","journal-title":"iScience"},{"key":"2279_CR13","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1002\/1521-4141(200107)31:7<2154::AID-IMMU2154>3.0.CO;2-U","volume":"31","author":"A Krug","year":"2001","unstructured":"Krug, A. et al. Identification of CpG oligonucleotide sequences with high induction of IFN-\u0251\/\u03b2 in plasmacytoid dendritic cells. Eur. J. Immunol. 31, 2154\u20132163 (2001).","journal-title":"Eur. J. Immunol."},{"key":"2279_CR14","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abc7302","volume":"6","author":"TJ Yun","year":"2021","unstructured":"Yun, T. J. et al. Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells. Sci. Immunol. 6, eabc7302 (2021).","journal-title":"Sci. Immunol."},{"key":"2279_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05784-3","volume":"9","author":"F Wimmers","year":"2018","unstructured":"Wimmers, F. et al. Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nat. Commun. 9, 3317 (2018).","journal-title":"Nat. Commun."},{"key":"2279_CR16","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.immuni.2007.07.013","volume":"27","author":"Y Kumagai","year":"2007","unstructured":"Kumagai, Y. et al. Alveolar macrophages are the primary interferon-\u0251 producer in pulmonary infection with RNA viruses. Immunity 27, 240\u2013252 (2007).","journal-title":"Immunity"},{"key":"2279_CR17","doi-asserted-by":"publisher","first-page":"20416","DOI":"10.1073\/pnas.0808537105","volume":"105","author":"S Scheu","year":"2008","unstructured":"Scheu, S., Dresing, P. & Locksley, R. M. Visualization of IFN\u03b2 production by plasmacytoid versus conventional dendritic cells under specific stimulation conditions in vivo. Proc. Natl Acad. Sci. USA 105, 20416\u201320421 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2279_CR18","doi-asserted-by":"publisher","first-page":"4447","DOI":"10.4049\/jimmunol.1500383","volume":"196","author":"J Bauer","year":"2016","unstructured":"Bauer, J. et al. Cutting edge: IFN-\u03b2 expression in the spleen is restricted to a subpopulation of plasmacytoid dendritic cells exhibiting a specific immune modulatory transcriptome signature. J. Immunol. 196, 4447\u20134451 (2016).","journal-title":"J. Immunol."},{"key":"2279_CR19","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201798836","volume":"37","author":"E Tomasello","year":"2018","unstructured":"Tomasello, E. et al. Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection. EMBO J. 37, e98836 (2018).","journal-title":"EMBO J."},{"key":"2279_CR20","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41590-020-0731-4","volume":"21","author":"A Abbas","year":"2020","unstructured":"Abbas, A. et al. The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection. Nat. Immunol. 21, 983\u2013997 (2020).","journal-title":"Nat. Immunol."},{"key":"2279_CR21","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1084\/jem.20021031","volume":"196","author":"M O\u2019Keeffe","year":"2002","unstructured":"O\u2019Keeffe, M. et al. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8+ dendritic cells only after microbial stimulus. J. Exp. Med. 196, 1307\u20131319 (2002).","journal-title":"J. Exp. Med."},{"key":"2279_CR22","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.4049\/jimmunol.1000454","volume":"186","author":"P Bjorck","year":"2011","unstructured":"Bjorck, P., Leong, H. X. & Engleman, E. G. Plasmacytoid dendritic cell dichotomy: identification of IFN-\u0251 producing cells as a phenotypically and functionally distinct subset. J. Immunol. 186, 1477\u20131485 (2011).","journal-title":"J. Immunol."},{"key":"2279_CR23","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1002\/eji.201343498","volume":"43","author":"M Niederquell","year":"2013","unstructured":"Niederquell, M. et al. Sca-1 expression defines developmental stages of mouse pDCs that show functional heterogeneity in the endosomal but not lysosomal TLR9 response. Eur. J. Immunol. 43, 2993\u20133005 (2013).","journal-title":"Eur. J. Immunol."},{"key":"2279_CR24","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/mi.2016.99","volume":"10","author":"M Swiecki","year":"2017","unstructured":"Swiecki, M. et al. Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state. Mucosal Immunol. 10, 936\u2013945 (2017).","journal-title":"Mucosal Immunol."},{"key":"2279_CR25","doi-asserted-by":"publisher","first-page":"6815","DOI":"10.4049\/jimmunol.0802008","volume":"182","author":"T Matsui","year":"2009","unstructured":"Matsui, T. et al. CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J. Immunol. 182, 6815\u20136823 (2009).","journal-title":"J. Immunol."},{"key":"2279_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.814627","volume":"13","author":"MH Ghanem","year":"2022","unstructured":"Ghanem, M. H. et al. Proteomic and single-cell transcriptomic dissection of human plasmacytoid dendritic cell response to influenza virus. Front. Immunol. 13, 814627 (2022).","journal-title":"Front. Immunol."},{"key":"2279_CR27","doi-asserted-by":"publisher","first-page":"e20231809","DOI":"10.1084\/jem.20231809","volume":"222","author":"Y Du","year":"2025","unstructured":"Du, Y. et al. Altered X-chromosome inactivation of the TLR7\/8 locus and heterogeneity of pDCs in systemic sclerosis. J. Exp. Med. 222, e20231809 (2025).","journal-title":"J. Exp. Med."},{"key":"2279_CR28","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai8071","volume":"2","author":"A Silvin","year":"2017","unstructured":"Silvin, A. et al. Constitutive resistance to viral infection in human CD141+ dendritic cells. Sci. Immunol. 2, eaai8071 (2017).","journal-title":"Sci. Immunol."},{"key":"2279_CR29","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.4049\/jimmunol.1400215","volume":"193","author":"T Frenz","year":"2014","unstructured":"Frenz, T. et al. Independent of plasmacytoid dendritic cell (pDC) infection, pDC triggered by virus-infected cells mount enhanced type I IFN responses of different composition as opposed to pDC stimulated with free virus. J. Immunol. 193, 2496\u20132503 (2014).","journal-title":"J. Immunol."},{"key":"2279_CR30","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/s41590-018-0136-9","volume":"19","author":"PF Rodrigues","year":"2018","unstructured":"Rodrigues, P. F. et al. Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells. Nat. Immunol. 19, 711\u2013722 (2018).","journal-title":"Nat. Immunol."},{"key":"2279_CR31","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41590-019-0420-3","volume":"20","author":"RJ Dress","year":"2019","unstructured":"Dress, R. J. et al. Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage. Nat. Immunol. 20, 852\u2013864 (2019).","journal-title":"Nat. Immunol."},{"key":"2279_CR32","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.immuni.2022.01.016","volume":"55","author":"J Feng","year":"2022","unstructured":"Feng, J. et al. Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells. Immunity 55, 405\u2013422 (2022).","journal-title":"Immunity"},{"key":"2279_CR33","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.4049\/jimmunol.2400227","volume":"213","author":"NJ Parekh","year":"2024","unstructured":"Parekh, N. J., Winship, D., Van Dis, E. & Stetson, D. B. Regulation and dynamics of IFN-\u03b2 expression revealed with a knockin reporter mouse. J. Immunol. 213, 1858\u20131868 (2024).","journal-title":"J. Immunol."},{"key":"2279_CR34","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41577-021-00577-0","volume":"22","author":"NA Lind","year":"2022","unstructured":"Lind, N. A., Rael, V. E., Pestal, K., Liu, B. & Barton, G. M. Regulation of the nucleic acid-sensing Toll-like receptors. Nat. Rev. Immunol. 22, 224\u2013235 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"2279_CR35","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.cell.2020.04.022","volume":"181","author":"L Schaupp","year":"2020","unstructured":"Schaupp, L. et al. Microbiota-induced type I interferons instruct a poised basal state of dendritic cells. Cell 181, 1080\u20131096 (2020).","journal-title":"Cell"},{"key":"2279_CR36","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.cell.2020.10.047","volume":"183","author":"KL Stefan","year":"2020","unstructured":"Stefan, K. L., Kim, M. V., Iwasaki, A. & Kasper, D. L. Commensal microbiota modulation of natural resistance to virus infection. Cell 183, 1312\u20131324 (2020).","journal-title":"Cell"},{"key":"2279_CR37","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.immuni.2022.04.006","volume":"55","author":"SF Erttmann","year":"2022","unstructured":"Erttmann, S. F. et al. The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis. Immunity 55, 847\u2013861 (2022).","journal-title":"Immunity"},{"key":"2279_CR38","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1084\/jem.20041930","volume":"201","author":"C Asselin-Paturel","year":"2005","unstructured":"Asselin-Paturel, C. et al. Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J. Exp. Med. 201, 1157\u20131167 (2005).","journal-title":"J. Exp. Med."},{"key":"2279_CR39","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.immuni.2012.05.020","volume":"37","author":"SC Ganal","year":"2012","unstructured":"Ganal, S. C. et al. Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37, 171\u2013186 (2012).","journal-title":"Immunity"},{"key":"2279_CR40","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.cell.2020.06.029","volume":"182","author":"ES Winkler","year":"2020","unstructured":"Winkler, E. S. et al. The intestinal microbiome restricts alphavirus infection and dissemination through a bile acid-type I IFN signaling axis. Cell 182, 901\u2013918 (2020).","journal-title":"Cell"},{"key":"2279_CR41","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1084\/jem.20011666","volume":"195","author":"W Barchet","year":"2002","unstructured":"Barchet, W. et al. Virus-induced interferon \u0251 production by a dendritic cell subset in the absence of feedback signaling in vivo. J. Exp. Med. 195, 507\u2013516 (2002).","journal-title":"J. Exp. Med."},{"key":"2279_CR42","doi-asserted-by":"publisher","first-page":"e1006195","DOI":"10.1371\/journal.ppat.1006195","volume":"13","author":"E Kindler","year":"2017","unstructured":"Kindler, E. et al. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication. PLoS Pathog. 13, e1006195 (2017).","journal-title":"PLoS Pathog."},{"key":"2279_CR43","doi-asserted-by":"publisher","first-page":"4044","DOI":"10.1073\/pnas.1417620112","volume":"112","author":"EM Carrington","year":"2015","unstructured":"Carrington, E. M. et al. Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells. Proc. Natl Acad. Sci. USA 112, 4044\u20134049 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2279_CR44","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1111\/imcb.12173","volume":"96","author":"C Marsman","year":"2018","unstructured":"Marsman, C. et al. Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation. Immunol. Cell Biol. 96, 1083\u20131094 (2018).","journal-title":"Immunol. Cell Biol."},{"key":"2279_CR45","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41590-017-0012-z","volume":"19","author":"SG Alculumbre","year":"2018","unstructured":"Alculumbre, S. G. et al. Diversification of human plasmacytoid predendritic cells in response to a single stimulus. Nat. Immunol. 19, 63\u201375 (2018).","journal-title":"Nat. Immunol."},{"key":"2279_CR46","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41586-024-07066-z","volume":"627","author":"C Weng","year":"2024","unstructured":"Weng, C. et al. Deciphering cell states and genealogies of human haematopoiesis. Nature 627, 389\u2013398 (2024).","journal-title":"Nature"},{"key":"2279_CR47","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.immuni.2012.07.018","volume":"37","author":"P Yu","year":"2012","unstructured":"Yu, P. et al. Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 37, 867\u2013879 (2012).","journal-title":"Immunity"},{"key":"2279_CR48","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1084\/jem.20110654","volume":"208","author":"M Swiecki","year":"2011","unstructured":"Swiecki, M. et al. Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J. Exp. Med. 208, 2367\u20132374 (2011).","journal-title":"J. Exp. Med."},{"key":"2279_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.605930","volume":"12","author":"M Motwani","year":"2021","unstructured":"Motwani, M. et al. cGAS-STING pathway does not promote autoimmunity in murine models of SLE. Front. Immunol. 12, 605930 (2021).","journal-title":"Front. Immunol."},{"key":"2279_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19918-z","volume":"11","author":"A Psarras","year":"2020","unstructured":"Psarras, A. et al. Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity. Nat. Commun. 11, 6149 (2020).","journal-title":"Nat. Commun."},{"key":"2279_CR51","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.chom.2008.08.016","volume":"4","author":"EI Zuniga","year":"2008","unstructured":"Zuniga, E. I., Liou, L. Y., Mack, L., Mendoza, M. & Oldstone, M. B. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe 4, 374\u2013386 (2008).","journal-title":"Cell Host Microbe"},{"key":"2279_CR52","doi-asserted-by":"publisher","first-page":"7178","DOI":"10.4049\/jimmunol.0802526","volume":"182","author":"LN Lee","year":"2009","unstructured":"Lee, L. N., Burke, S., Montoya, M. & Borrow, P. Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice. J. Immunol. 182, 7178\u20137189 (2009).","journal-title":"J. Immunol."},{"key":"2279_CR53","doi-asserted-by":"publisher","first-page":"5188","DOI":"10.1158\/0008-5472.CAN-11-3468","volume":"72","author":"V Sisirak","year":"2012","unstructured":"Sisirak, V. et al. Impaired IFN-\u0251 production by plasmacytoid dendritic cells favors regulatory T-cell expansion that may contribute to breast cancer progression. Cancer Res. 72, 5188\u20135197 (2012).","journal-title":"Cancer Res."},{"key":"2279_CR54","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1084\/jem.20160189","volume":"213","author":"H Schmitt","year":"2016","unstructured":"Schmitt, H. et al. Siglec-H protects from virus-triggered severe systemic autoimmunity. J. Exp. Med. 213, 1627\u20131644 (2016).","journal-title":"J. Exp. Med."},{"key":"2279_CR55","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.immuni.2015.07.009","volume":"43","author":"A Bunin","year":"2015","unstructured":"Bunin, A. et al. Protein tyrosine phosphatase PTPRS is an inhibitory receptor on human and murine plasmacytoid dendritic cells. Immunity 43, 277\u2013288 (2015).","journal-title":"Immunity"},{"key":"2279_CR56","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1084\/jem.20021522","volume":"197","author":"M Dalod","year":"2003","unstructured":"Dalod, M. et al. Dendritic cell responses to early murine cytomegalovirus infection: subset functional specialization and differential regulation by interferon \u0251\/\u03b2. J. Exp. Med. 197, 885\u2013898 (2003).","journal-title":"J. Exp. Med."},{"key":"2279_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01687-x","volume":"8","author":"SI Saitoh","year":"2017","unstructured":"Saitoh, S. I. et al. TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells. Nat. Commun. 8, 1592 (2017).","journal-title":"Nat. Commun."},{"key":"2279_CR58","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/eji.201343806","volume":"44","author":"S Kim","year":"2014","unstructured":"Kim, S. et al. Self-priming determines high type I IFN production by plasmacytoid dendritic cells. Eur. J. Immunol. 44, 807\u2013818 (2014).","journal-title":"Eur. J. Immunol."},{"key":"2279_CR59","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1016\/j.celrep.2018.11.030","volume":"25","author":"MB Uccellini","year":"2018","unstructured":"Uccellini, M. B. & Garcia-Sastre, A. ISRE-reporter mouse reveals high basal and induced type I IFN responses in inflammatory monocytes. Cell Rep. 25, 2784\u20132796 (2018).","journal-title":"Cell Rep."},{"key":"2279_CR60","doi-asserted-by":"publisher","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","volume":"20","author":"S Jung","year":"2000","unstructured":"Jung, S. et al. Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20, 4106\u20134114 (2000).","journal-title":"Mol. Cell. Biol."},{"key":"2279_CR61","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.immuni.2020.04.015","volume":"52","author":"C Soni","year":"2020","unstructured":"Soni, C. et al. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. Immunity 52, 1022\u20131038 (2020).","journal-title":"Immunity"},{"key":"2279_CR62","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.4049\/jimmunol.174.5.2499","volume":"174","author":"A Mathian","year":"2005","unstructured":"Mathian, A., Weinberg, A., Gallegos, M., Banchereau, J. & Koutouzov, S. IFN-\u0251 induces early lethal lupus in preautoimmune (New Zealand Black x New Zealand White)F1 but not in BALB\/c mice. J. Immunol. 174, 2499\u20132506 (2005).","journal-title":"J. Immunol."},{"key":"2279_CR63","first-page":"3239","volume":"60","author":"N Mach","year":"2000","unstructured":"Mach, N. et al. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res. 60, 3239\u20133246 (2000).","journal-title":"Cancer Res."},{"key":"2279_CR64","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1084\/jem.20072390","volume":"205","author":"MJ Turner","year":"2008","unstructured":"Turner, M. J., Jellison, E. R., Lingenheld, E. G., Puddington, L. & Lefrancois, L. Avidity maturation of memory CD8 T cells is limited by self-antigen expression. J. Exp. Med. 205, 1859\u20131868 (2008).","journal-title":"J. Exp. Med."},{"key":"2279_CR65","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1128\/JVI.78.3.1150-1159.2004","volume":"78","author":"MM Chua","year":"2004","unstructured":"Chua, M. M., MacNamara, K. C., San Mateo, L., Shen, H. & Weiss, S. R. Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants. J. Virol. 78, 1150\u20131159 (2004).","journal-title":"J. Virol."},{"key":"2279_CR66","doi-asserted-by":"publisher","first-page":"eabg0505","DOI":"10.1126\/sciadv.abg0505","volume":"7","author":"E Becht","year":"2021","unstructured":"Becht, E. et al. High-throughput single-cell quantification of hundreds of proteins using conventional flow cytometry and machine learning. Sci. Adv. 7, eabg0505 (2021).","journal-title":"Sci. Adv."},{"key":"2279_CR67","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902 (2019).","journal-title":"Cell"},{"key":"2279_CR68","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587 (2021).","journal-title":"Cell"},{"key":"2279_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/srep22675","volume":"6","author":"JA van Buggenum","year":"2016","unstructured":"van Buggenum, J. A. et al. A covalent and cleavable antibody-DNA conjugation strategy for sensitive protein detection via immuno-PCR. Sci. Rep. 6, 22675 (2016).","journal-title":"Sci. Rep."},{"key":"2279_CR70","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1038\/nmeth.4380","volume":"14","author":"M Stoeckius","year":"2017","unstructured":"Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865\u2013868 (2017).","journal-title":"Nat. Methods"},{"key":"2279_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1603-1","volume":"19","author":"M Stoeckius","year":"2018","unstructured":"Stoeckius, M. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018).","journal-title":"Genome Biol."},{"key":"2279_CR72","doi-asserted-by":"publisher","unstructured":"Khodadadi-Jamayran, A. et al. iCellR: combined coverage correction and principal component alignment for batch alignment in single-cell sequencing analysis. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2020.03.31.019109 (2020).","DOI":"10.1101\/2020.03.31.019109"},{"key":"2279_CR73","doi-asserted-by":"crossref","unstructured":"McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https:\/\/arxiv.org\/abs\/1802.03426 (2018).","DOI":"10.21105\/joss.00861"},{"key":"2279_CR74","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/ni1008-1091","volume":"9","author":"TS Heng","year":"2008","unstructured":"Heng, T. S. et al. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091\u20131094 (2008).","journal-title":"Nat. Immunol."},{"key":"2279_CR75","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","volume":"560","author":"G La Manno","year":"2018","unstructured":"La Manno, G. et al. RNA velocity of single cells. Nature 560, 494\u2013498 (2018).","journal-title":"Nature"},{"key":"2279_CR76","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z","volume":"9","author":"VA Traag","year":"2019","unstructured":"Traag, V. A., Waltman, L. & van Eck, N. J. From Louvain to Leiden: guaranteeing well-connected communities. Sci. Rep. 9, 5233 (2019).","journal-title":"Sci. Rep."},{"key":"2279_CR77","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.immuni.2017.02.019","volume":"46","author":"T Granot","year":"2017","unstructured":"Granot, T. et al. Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity 46, 504\u2013515 (2017).","journal-title":"Immunity"},{"key":"2279_CR78","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/ajt.14434","volume":"18","author":"DJ Carpenter","year":"2018","unstructured":"Carpenter, D. J. et al. Human immunology studies using organ donors: impact of clinical variations on immune parameters in tissues and circulation. Am. J. Transpl. 18, 74\u201388 (2018).","journal-title":"Am. J. Transpl."},{"key":"2279_CR79","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.cell.2018.07.010","volume":"174","author":"Y Goltsev","year":"2018","unstructured":"Goltsev, Y. et al. Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell 174, 968\u2013981 (2018).","journal-title":"Cell"}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-025-02279-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-025-02279-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-025-02279-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T14:44:18Z","timestamp":1764341058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-025-02279-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":79,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["2279"],"URL":"https:\/\/doi.org\/10.1038\/s41590-025-02279-4","relation":{},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"14 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article was originally published under standard Springer Nature license (\u00a9 The Author(s), under exclusive licence to Springer Nature America, Inc.). It is now available as an open-access paper under a Creative Commons Attribution 4.0 International license, \u00a9 The Author(s). The copyright has been amended in the HTML and PDF versions of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.S. and P.S. are inventors on a patent related to the CITE-seq method and are or have been employed by 10x Genomics, Inc., but were not affiliated with it or any other commercial entity at the time of the work described in this paper. B.R. is an advisor for Related Sciences and a co-founder of Danger Bio. J.I. serves on the advisory board of Immunitas Therapeutics. None of these affiliations are related to the present work. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}