Aarhus University, Denmark
Student: Georgios Katzilieris-Petras, M.Pharm., Ph.D. student
Supervisor: Prof. Søren Riis Paludan, Ph.D.
Co-supervisor: Assoc. Prof. Line Reinert, Ph.D.
Herpes simplex virus 1 (HSV-1) is a DNA virus known to primarily cause oral vesicular lesions and establish latency in the peripheral nervous system. However, in immunocompromised patients and neonates, it can cause a severe infection of the central nervous system (CNS), called herpes simplex encephalitis (HSE). This disease can lead to severe complications, such as inflammation, oedema and haemorrhage of the brain, and eventually death. Although the late stages of the disease have been thoroughly investigated, it still remains unknown how the immune cells of the brain are recruited to the sites of infection in order to limit viral spreading during the early and most damaging phase of the disease. Our hypothesis is that resident immune cells in the brain receive one or more signals from infected brain cells, become activated and are recruited to the major sites of infection.
In this research project, we will use an in vivo mouse model to simulate and study the early stages of HSE. To delineate the signalling pathways responsible for cell recruitment, we will use knockout mice that lack essential factors for HSV-1 detection and activation of the innate immune system. Various techniques (RT-qPCR, ELISA, flow cytometry, immunocytochemistry) will be used to characterize the behaviour and interaction matrix between brain cells that lead to the recruitment of different types of cells, such as brain macrophages, to the sites of infection. To further validate our hypothesis, primary brain cells will be cultured in vitro, and we will investigate their responses after HSV-1 infection.
Ultimately, these approaches will help us to delineate the key elements of cellular recruitment and crosstalk after HSV-1 sensing in the CNS in order to gain a clearer understanding of the immune responses during the early stages of HSE.
Søren Riis Paludan, Professor
Department of Biomedicine