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- W4313374484 abstract "Abstract Type I interferons (IFN-I) play a critical role in shaping the antiviral immune response early after an infection. However, the dynamics by which different immune cell subsets regulate the IFN-I response during the early stages of acute and chronic infections is not completely understood. Here we used the Lymphocytic Choriomeningitis Virus (LCMV)-infection mouse model system to characterize the dynamics of the IFN-I response in acute and chronic infections. Time-resolved spleen-transcriptomes revealed that during an acute infection, IFN-I showed two peaks of expression at days 2 and 5 post-infection. In contrast, in chronically infected mice a single peak of IFN-I genes appeared at day 1. Further analysis revealed that IFN-I genes in acute infection were co-expressed with genes related to inflammatory macrophages, suggesting an important role of these cells determining infection fate. Indeed, we identified metallophilic macrophages as an important source of Ifnb only during acute infection and demonstrated that the subsequent IFN-I receptor (IFNAR) signaling is necessary to induce pro-inflammatory macrophages. In contrast, during chronic infection, early depletion of marginal zone macrophages results in a lack of IFN-I production and the inflammatory response is not induced. Importantly, blockage of the second peak of IFN-I response by IFNAR blockage during an acute infection also resulted in exhaustion of virus-specific CD8 T cells and prevention of lymphoid tissue fibrosis. Further studies are ongoing to decipher the regulatory mechanisms underlying the characterized events, thus revealing universal concepts related to infection fate decisions that are also relevant for persistent human infections such as HIV or HCV." @default.
- W4313374484 created "2023-01-06" @default.
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- W4313374484 date "2020-05-01" @default.
- W4313374484 modified "2023-10-06" @default.
- W4313374484 title "The spatiotemporal dynamics of type I IFN response determine viral infection outcome" @default.
- W4313374484 doi "https://doi.org/10.4049/jimmunol.204.supp.75.12" @default.
- W4313374484 hasPublicationYear "2020" @default.
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