A ceramide analogue stimulates dendritic cells to promote T cell responses upon virus infections

A ceramide analogue stimulates dendritic cells to promote T cell responses upon virus infections

The ceramide family of lipids plays important roles in both cell structure and signaling in a diverse array of cell types, including immune cells. However, very little is known regarding how ceramide affects the activation of dendritic cells (DCs) in response to viral infection. In this study, we de...

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Bibliographic Details
Published in:The Journal of immunology (1950) Vol. 194; no. 9; pp. 4339 - 4349
Main Authors: Pritzl, Curtis J, Seo, Young-Jin, Xia, Chuan, Vijayan, Madhuvanthi, Stokes, Zachary D, Hahm, Bumsuk
Format: Journal Article
Language:English
Published: United States 01-05-2015
Subjects:
Animals
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Ceramides - pharmacology
Cytotoxicity, Immunologic - drug effects
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Disease Models, Animal
Immunologic Factors - pharmacology
Immunomodulation - drug effects
Influenza virus
Lymphocyte Activation
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - metabolism
Lymphocytic choriomeningitis virus
Lymphocytic choriomeningitis virus - immunology
Mice
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - metabolism
T-Lymphocyte Subsets - drug effects
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Virus Diseases - immunology
Virus Diseases - metabolism
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Summary:The ceramide family of lipids plays important roles in both cell structure and signaling in a diverse array of cell types, including immune cells. However, very little is known regarding how ceramide affects the activation of dendritic cells (DCs) in response to viral infection. In this study, we demonstrate that a synthetic ceramide analog (C8) stimulates DCs to increase the expansion of virus-specific T cells upon virus infection. Exogenously supplied C8 ceramide elevated the expression of DC maturation markers such as MHC class I and costimulatory molecules following infection with the clone 13 strain of lymphocytic choriomeningitis virus (LCMV) or influenza virus. Importantly, ceramide-conditioned, LCMV-infected DCs displayed an increased ability to promote expansion of virus-specific CD8(+) T cells when compared with virus-infected DCs. Furthermore, a locally instilled ceramide analog significantly increased virus-reactive T cell responses in vivo to both LCMV and influenza virus infections. Collectively, these findings provide new insights into ceramide-mediated regulation of DC responses against virus infection and help us establish a foundation for novel immune-stimulatory therapeutics.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1402672