title: A ceramide analogue stimulates dendritic cells to promote T cell responses upon virus infections.
abstract: 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.
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.
authors: Curtis J
authors: CJ
authors: Pritzl
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.
authors: Young-Jin
authors: YJ
authors: Seo
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.
authors: Chuan
authors: C
authors: Xia
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.
authors: Madhuvanthi
authors: M
authors: Vijayan
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212.
authors: Zachary D
authors: ZD
authors: Stokes
authors: Department of Surgery, University of Missouri, Columbia, MO 65212; andDepartment of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212 hahmb@health.missouri.edu.
authors: Bumsuk
authors: B
authors: Hahm
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism*
chemical_list: D002518:Ceramides; D007155:Immunologic Factors