DNGR-1 is dispensable for CD8+ T-cell priming during respiratory syncytial virus infection.
During respiratory syncytial virus (RSV) infection CD8(+) T cells both assist in viral clearance and contribute to immunopathology. CD8(+) T cells recognize viral peptides presented by dendritic cells (DCs), which can directly present viral antigens when infected or, alternatively, "cross-present" antigens after endocytosis of dead or dying infected cells. Mouse CD8α(+) and CD103(+) DCs excel at cross-presentation, in part because they express the receptor DNGR-1 that detects dead cells by binding to exposed F-actin and routes internalized cell debris into the cross-presentation pathway. As RSV causes death in infected epithelial cells, we tested whether cross-presentation via DNGR-1 is necessary for CD8(+) T-cell responses to the virus. DNGR-1-deficient or wild-type mice were intranasally inoculated with RSV and the magnitude of RSV-specific CD8(+) T-cell induction was measured. We found that during live RSV infection, cross-presentation via DNGR-1 did not have a major role in the generation of RSV-specific CD8(+) T-cell responses. However, after intranasal immunization with dead cells infected with RSV, a dependence on DNGR-1 for RSV-specific CD8(+) T-cell responses was observed, confirming the ascribed role of the receptor. Thus, direct presentation by DCs may be the major pathway initiating CD8(+) T-cell responses to RSV, while DNGR-1-dependent cross-presentation has no detectable role.
Centre for Respiratory Infections, Section of Respiratory Infections, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
Lydia R
LR
Durant
Catherine
C
Pereira
Aime
A
Boakye
Spyridon
S
Makris
Fahima
F
Kausar
Michelle
M
Goritzka
Cecilia
C
Johansson
D000199:Actins / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D037181:Lectins, C-Type / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D019562:Viral Load / Q000276:immunology
D000199:Actins; D000956:Antigens, Viral; C529914:Clec9a protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic
CD8+ T cell; Cross-presentation; DNGR-1; Lung infection; Virus