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Both plasmacytoid dendritic cells and monocytes stimulate natural killer cells early during human herpes simplex virus type 1 infections
Author(s) -
Vogel Karin,
Thomann Sabrina,
Vogel Benjamin,
Schuster Philipp,
Schmidt Barbara
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12337
Subject(s) - biology , herpes simplex virus , secretion , tumor necrosis factor alpha , degranulation , virology , monocyte , immunology , peripheral blood mononuclear cell , interferon , effector , interleukin 12 , plasmacytoid dendritic cell , virus , dendritic cell , immune system , cytotoxic t cell , receptor , in vitro , biochemistry
Summary Herpes simplex virus type 1 ( HSV ‐1), a member of the herpes virus family, is characterized by a short replication cycle, high cytopathogenicity and distinct neurotropism. Primary infection and reactivation may cause severe diseases in immunocompetent and immunosuppressed individuals. This study investigated the role of human plasmacytoid dendritic cells (p DC ) in the activation of natural killer ( NK ) cells for the control of herpesviral infections. Within peripheral blood mononuclear cells, UV ‐inactivated HSV ‐1 and C p G ‐ A induced CD 69 up‐regulation on NK cells, whereas infectious HSV ‐1 was particularly active in inducing NK cell effector functions interferon‐ γ ( IFN ‐ γ ) secretion and degranulation. The p DC ‐derived IFN ‐ α significantly contributed to NK cell activation, as evident from neutralization and cell depletion experiments. In addition, monocyte‐derived tumour necrosis factor‐ α ( TNF ‐ α ) induced after exposure to infectious HSV ‐1 was found to stimulate IFN ‐ γ secretion. A minority of monocytes was shown to be non‐productively infected in experiments using fluorescently labelled viruses and quantitative PCR analyses. HSV ‐1‐exposed monocytes up‐regulated classical HLA ‐ ABC and non‐classical HLA ‐ E molecules at the cell surface in an IFN ‐ α ‐dependent manner, whereas stress molecules MICA / B were not induced. Notably, depletion of monocytes reduced NK cell effector functions induced by infectious HSV ‐1 ( P < 0·05). Altogether, our data suggest a model in which HSV ‐1‐stimulated p DC and monocytes activate NK cells via secretion of IFN ‐ α and TNF ‐ α . In addition, infection of monocytes induces NK cell effector functions via TNF ‐ α ‐dependent and TNF ‐ α ‐independent mechanisms. Hence, p DC and monocytes, which are among the first cells infiltrating herpetic lesions, appear to have important bystander functions for NK cells to control these viral infections.