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oai:recercat.cat:20.500.12327/28552025-10-22T11:24:14Zcom_2072_4428com_2072_4427col_2072_487898

Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation Casella, Valentina Domenjo-Vila, Eva Esteve-Codina, Anna Pedragosa, Mireia Cebollada Rica, Paula Vidal, Enric de la Rubia, Ivan López-Rodríguez, Cristina Bocharov, Gennady Argilaguet, Jordi Meyerhans, Andreas Producció Animal Sanitat Animal 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 wellcoordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism. 2025-10-22T11:24:14Z 2025-10-22T11:24:14Z 2025-10-22T11:24:14Z 2023-12-18 info:eu-repo/semantics/article Casella, Valentina, Eva Domenjo-Vila, Anna Esteve‐Codina, Mireia Pedragosa, Paula Cebollada Rica, Enríc Vidal, Ivan De La Rubia, et al. 2023. “Differential Kinetics of Splenic CD169+ Macrophage Death Is One Underlying Cause of Virus Infection Fate Regulation.” Cell Death and Disease 14 (12): 838. doi:10.1038/s41419-023-06374-y. 2041-4889 http://hdl.handle.net/20.500.12327/2855 https://doi.org/10.1038/s41419-023-06374-y eng Cell Death and Disease MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-106323RB-I00/ES/Characterization and manipulation of control points of virus infection fates/ MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2022-141395OB-I00/ES/COORDINACION Y COOPERACION DE CELULAS INMUNES DURANTE INFECCIONES VIRALES AGUDAS Y CRONICAS/ MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/CEX2018-000792-M/ES/ / ISCIII/ /PT17-0009-0019/ES/ / FEDER/ / /EU/ / http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Attribution 4.0 International Springer Nature