Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation
View/Open
Author
Casella, Valentina
Domenjo-Vila, Eva
Esteve-Codina, Anna
Pedragosa, Mireia
Cebollada Rica, Paula
de la Rubia, Ivan
López-Rodríguez, Cristina
Bocharov, Gennady
Meyerhans, Andreas
Publication date
2023-12-18ISSN
2041-4889
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 wellcoordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
13
Publisher
Springer Nature
Is part of
Cell Death and Disease
Citation
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.
Grant agreement number
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/ /
Program
Sanitat Animal
This item appears in the following Collection(s)
- ARTICLES CIENTÍFICS [2555]
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/