Herpes simplex virus-mediated skin infections: cytokines and its interplay

The skin, as the first physical barrier for invading pathogens, also serves as an immunologically active organ. Breaching the skin barrier is thus essential for pathogens to enter the body. The skin contains various immune responsive cells that initiate both the innate and adaptive immune response upon invasion. Activated immune cells help to regulate cytokine response and their differentiation to promote or suppress the crucial immune response against invading pathogens. Human herpes simplex viruses (HHSVs) are the oldest pathogen that can escape immune surveillance of the human host by a well-developed escape mechanism within ganglia, as their evolutionary strategy. In primary infection, a non-specific defense of the host initiates the response against the invading virion. The initial direct antiviral action of the host is regulated by activated macrophages, via the release of cytokines like tumor necrosis factor (TNF), and type-1 interferon (IFN-1). The host-derived cytokines including IFN-12, TNF, and IFN-1 in turn induce natural killer (NK) cells to release IFN-γ. Their positive feedback with synergistic interactions collectively releases nitric oxide (NO) and reactive oxygen species (ROS) against the invading virus. Simultaneously, the combination of cytokines, macrophages, and other cells activates the immune system to eliminate the pathogen. However, the virus has also evolved various mechanisms to counter the host defense strategies. This review will highlight virus-mediated skin infections, especially by HSV, and portray a detailed role of virus-induced cytokines in host-immunity to challenge the invading virion during mucocutaneous HSV infection. Further, this review will discuss the viral-interference on host defense to provide a simplistic overview of the complications of cutaneous HSV infection.