Herpes simplex virus infection of dendritic cells: balance among activation, inhibition, and immunity.
Several lines of evidence suggest that dendritic cells (DCs), the most potent antigen-presenting cells known, play a role in the immunological control of herpes simplex virus (HSV) infections. HSV infection of DCs induced submaximal maturation, but DCs failed to mature further in response to lipopolysaccharide (LPS). LPS induced interleukin (IL)-12 secretion, and the induction of primary and secondary T cell responses were impaired by infection. Ultimately, DC infection resulted in delayed, asynchronous apoptotic cell death. However, infected DCs induced HSV recall responses in some individuals. Furthermore, soluble factors secreted by DCs after infection induced DC maturation and primed for IL-12 secretion after LPS stimulation. These data support a pathogenetic model of HSV infection, in which initial delay in the generation of immune responses to HSV at peripheral sites is mediated by disruption of DC function but is overcome by bystander DC maturation and cross-presentation of HSV antigens.
Pollara
Gabriele
G
Department of Immunology and Molecular Pathology, University College London Hospitals, United Kingdom.
Speidel
Katharina
K
Samady
Laila
L
Rajpopat
Mansi
M
McGrath
Yvonne
Y
Ledermann
Jonathan
J
Coffin
Robert S
RS
Katz
David R
DR
Chain
Benjamin
B
D017209:Apoptosis; D002454:Cell Differentiation; D048429:Cell Size; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology
D008070:Lipopolysaccharides; D018664:Interleukin-12