Dysregulated expression of IFN‐γ and IL‐10 and impaired IFN‐γ‐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‐γ 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‐γ 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‐γ production by HSV‐2‐stimulated PBMCs. Enhanced production of IFN‐γ may modulate HSV replication and B7 expression on monocytic cells of HSV‐infected individuals. In contrast to seronegative controls, IFN‐γ 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‐γ 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‐γ at different disease stages and the impaired ability of monocytic cells to respond to IFN‐γ may play a role in the pathogenesis of recurrent genital herpes disease.