Innate and adaptive immunity against herpes simplex virus type 2 in the genital mucosa

Herpes simplex virus type 2 (HSV-2) is becoming increasingly prevalent worldwide, despite the widespread use of antiviral drugs. Its ability to evade the immune system and establish a latent infection has made it difficult to develop an effective vaccine. Our understanding of the immune response against HSV-2 remains complex and involves a balance between innate signaling pathways and the adaptive immune response. Primary infection with HSV-2 induces toll-like receptor (TLR)-mediated Type I interferon (IFN) production, which establishes an antiviral state and activates multiple cell types, including natural killer cells and plasmacytoid dendritic cells. This innate response is not only crucial for controlling initial infection, but also for priming adaptive immune responses as well. Both humoral and cellular responses encompass adaptive immunity, although the former has been shown to be dispensable in response to HSV-2. Recently, numerous studies have attributed IFNγ producing CD4(+) T cells to be the key effector molecule responsible for clearing infection. It remains unclear whether regulatory T (Treg) cells are a source of aid or hindrance in the clearance of disease. Collectively, this review highlights the balance between innate and adaptive effector responses that contribute to the control and clearance of HSV-2 infection.