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Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8+ T cell responses against an arthritogenic alphavirus
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Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8+ T cell responses against an arthritogenic alphavirus
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Journal Article
Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8+ T cell responses against an arthritogenic alphavirus
2024
Overview
Chronic arthritis and musculoskeletal disease are common outcomes of infections caused by arthritogenic alphaviruses, including Ross River virus (RRV), due to incomplete virus clearance. Unlike other viral infections that are efficiently cleared by cytotoxic CD8 + T cells, RRV infection is surprisingly unaffected by CD8 + T cells as mice lacking or having these cells show similar viral persistence in joint and lymphoid tissues. To elucidate the basis for this deficient response, we measured the RRV-specific CD8 + T-cell population size and activation state relative to another virus known to elicit a strong T-cell response. Our findings reveal that RRV induces fewer CD8 + T cells due to limited infection of immune cells in the draining lymph node. By increasing RRV susceptibility in antigen-presenting cells, we elicited a robust CD8 + T-cell response. These results highlight antigen availability and virus tropism as possible targets for intervention against RRV immune evasion and persistence.
Publisher
American Society for Microbiology
Subject
/ Alphavirus Infections - immunology
/ Alphavirus Infections - virology
/ Animals
/ Antigen Presentation - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Dendritic Cells - immunology
/ Epitopes
/ Epitopes, T-Lymphocyte - genetics
/ Epitopes, T-Lymphocyte - immunology
/ Interferon Type I - immunology
/ Lymphocytic choriomeningitis virus - immunology
/ Major histocompatibility complex
/ Mice
/ Peptides
/ RNA
/ Ross River virus - immunology
/ Spleen
/ T cells
/ Tropism
/ Virology
/ Viruses
