Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells.
HSV efficiently infects dendritic cells (DCs) in their immature state and induces down-regulation of costimulatory and adhesion molecules. As in mice, HSV infection of human DCs also leads to their rapid and progressive apoptosis, and we show that both early and late viral proteins contribute to its induction. Because topical HSV infection is confined to the epidermis, Langerhans cells are expected to be the major APCs in draining lymph nodes. However, recent observations in murine models show T cell activation to be mediated by nonepidermal DC subsets, suggesting cross-presentation of viral Ag. In this study we provide an explanation for this phenomenon, demonstrating that HSV-infected apoptotic DCs are readily phagocytosed by uninfected bystander DCs, which, in turn, stimulate virus-specific CD8+ T cell clones.
Bosnjak
Lidija
L
Center for Virus Research, Westmead Millennium Institutem, Westmead Millennium Institute and Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Australia.
Miranda-Saksena
Monica
M
Koelle
David M
DM
Boadle
Ross A
RA
Jones
Cheryl A
CA
Cunningham
Anthony L
AL
D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000648:ultrastructure / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000648:ultrastructure / Q000821:virology; D010587:Phagocytosis / Q000276:immunology; D017735:Virus Latency / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D017874:Immediate-Early Proteins