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Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation

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dc.contributor.author Casella, Valentina, 1991-
dc.contributor.author Domenjó Vila, Eva, 1993-
dc.contributor.author Esteve-Codina, Anna
dc.contributor.author Pedragosa Marín, Mireia, 1988-
dc.contributor.author Cebollada Rica, Paula
dc.contributor.author Vidal Barba, Enric
dc.contributor.author Rubia, Ivan de la
dc.contributor.author López Rodríguez, M. Cristina
dc.contributor.author Bocharov, Gennady A.
dc.contributor.author Argilaguet Marqués, Jordi, 1977-
dc.contributor.author Meyerhans, Andreas
dc.date.accessioned 2024-01-26T06:39:13Z
dc.date.available 2024-01-26T06:39:13Z
dc.date.issued 2023
dc.identifier.citation Casella V, Domenjo-Vila E, Esteve-Codina A, Pedragosa M, Cebollada Rica P, Vidal E, de la Rubia I, López-Rodríguez C, Bocharov G, Argilaguet J, Meyerhans A. Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation. Cell Death Dis. 2023 Dec 18;14(12):838. DOI: 10.1038/s41419-023-06374-y
dc.identifier.issn 2041-4889
dc.identifier.uri http://hdl.handle.net/10230/58823
dc.description.abstract Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation grant No. PID2019-106323RB-I00 AEI//10.13039/501100011033 and PID2022-141395OB-I00, the “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M), the Russian Science Foundation grant No. 23-11-00116 and the AEC funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Cell Death Dis. 2023 Dec 18;14(12):838
dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41419-023-06374-y
dc.subject.keyword Cell death and immune response
dc.subject.keyword Imaging the immune system
dc.subject.keyword Immune cell death
dc.subject.keyword Viral infection
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106323RB-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-141395OB-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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