Dysregulated expression of IFN-gamma and IL-10 and impaired IFN-gamma-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.
Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-gamma production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-gamma and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-gamma production by HSV-2-stimulated PBMCs. Enhanced production of IFN-gamma may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-gamma failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-gamma resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-gamma at different disease stages and the impaired ability of monocytic cells to respond to IFN-gamma may play a role in the pathogenesis of recurrent genital herpes disease.
Singh
R
R
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Kumar
A
A
Creery
W D
WD
Ruben
M
M
Giulivi
A
A
Diaz-Mitoma
F
F
D016022:Case-Control Studies; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis*; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D018417:Th1 Cells / Q000276:immunology*; D014775:Virus Activation; D014779:Virus Replication
D004279:DNA, Viral; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma