{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:54:35Z","timestamp":1782280475696,"version":"3.54.5"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"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. Microbiol."],"abstract":"<jats:p>African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2\u2009weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR\/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and <jats:italic>ex vivo<\/jats:italic> expression of IFN-\u03b3 on immune cells showed that T cells were transiently activated and expressed IFN-\u03b3 as early as 5\u2009days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1328177","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T04:26:06Z","timestamp":1707884766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Yunfei","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Qie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobin","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0065-2776(08)60654-9","article-title":"Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21)","volume":"46","author":"Ahearn","year":"1989","journal-title":"Adv. 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Res."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"S184","DOI":"10.1542\/peds.2014-1817JJJJ","article-title":"Cell death by Pyroptosis drives CD4 T-cell depletion in HIV-1 infection","volume":"134","author":"Church","year":"2014","journal-title":"Pediatrics"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3390\/v11040310","article-title":"African swine fever status in Europe","volume":"11","author":"Cwynar","year":"2019","journal-title":"Viruses"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1002\/embj.201488027","article-title":"Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming","volume":"33","author":"Dalod","year":"2014","journal-title":"EMBO J."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.virusres.2012.10.020","article-title":"African swine fever virus replication and genomics","volume":"173","author":"Dixon","year":"2013","journal-title":"Virus Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.virusres.2019.04.002","article-title":"African swine fever virus evasion of host defences","volume":"266","author":"Dixon","year":"2019","journal-title":"Virus Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.virusres.2018.10.007","article-title":"Infection, modulation and responses of antigen-presenting cells to African swine fever viruses","volume":"258","author":"Franzoni","year":"2018","journal-title":"Virus Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"445","DOI":"10.3390\/v11050445","article-title":"Porcine dendritic cells and viruses: an update","volume":"11","author":"Franzoni","year":"2019","journal-title":"Viruses"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.vetmic.2016.12.010","article-title":"Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets","volume":"198","author":"Franzoni","year":"2017","journal-title":"Vet. 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Virol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"77","DOI":"10.14670\/HH-19.77","article-title":"Apoptosis of thymocytes in experimental African swine fever virus infection","volume":"19","author":"Salguero","year":"2004","journal-title":"Histol. Histopathol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1128\/JVI.00350-20","article-title":"Absence of long-term protection in domestic pigs immunized with attenuated African swine fever virus isolate OURT88\/3 or BeninDeltaMGF correlates with increased levels of regulatory T cells and Interleukin-10","volume":"94","author":"Sanchez-Cordon","year":"2020","journal-title":"J. Virol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1111\/tbed.14048","article-title":"T-cell responses in domestic pigs and wild boar upon infection with the moderately virulent African swine fever virus strain 'Estonia2014'","volume":"68","author":"Schafer","year":"2021","journal-title":"Transbound. Emerg. 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