Tick ThaNK · Tick-borne encephalitis Targeted by Human Active NK cells

Tick-borne encephalitis Targeted by Human Active NK cells

Natural killer (NK) cells are important players during the immune response against viral infections. However, their role in tick borne encephalitis (TBE) and other viral infections in the central nervous system (CNS) has been understudied. The aim of this project was to understand how NK cells fight the infection produced by the tick-borne encephalitis virus (TBEV) that may cause brain inflammation and long-term neurological sequelae. We also studied what NK cells do in the CNS and what are the mechanisms of their migration into the brain during TBEV infection. We think that a better understanding of the mechanisms responsible for NK cell activation and recruitment to the site of infection in this particular disease can give us a glimpse of the possible function of NK cells during other viral infections that affect the CNS. The European TBEV causes a mortality rate of 1-2% and deaths occur in average one week after the onset of neurological signs and symptoms. The Far-Eastern TBEV strain is more severe, and the mortality rate rises up to 5-20%.TBE may cause a long recovery period, leaving long-term or even permanent neurologic sequelae in 30 to 60% of patients with the disease. TBE is a disease occurring in different areas within Europe and Asia and is transmitted by the bite of an infected tick. The incubation period takes in average seven days after the bite of an infected tick. Most of the TBEV infections are asymptomatic, however those who develop symptoms show a clinical debut with a biphasic pattern. Unspecific symptoms such as fever, headache, myalgia and nausea appear during the first phase that lasts from 2-10 days. An asymptomatic period follows and subsequently, a second phase with neurological involvement occurs producing meningitis, encephalitis or meningoencephalitis. Since there is no cure or specific treatment for TBE, hospitalization, supportive care, use of anti-inflammatory drugs such as corticosteroids, intubation and/or ventilator support may be considered based on disease severity. NK cells constitute a first line of defense against viral infections and tumors. According to the expression of the CD56 molecule on their surface, NK cells are classified into two main subsets, both with specific functions and locations within the body. The CD56dim NK cell population is predominant in peripheral blood and has a cytotoxic function, whereas the CD56bright immunoregulatory subset is mainly found in peripheral and lymphoid tissues. Recently, the field of tissue resident NK cells (trNK) in solid organs and their function in tissue development and remodeling have gained increasing interest. However, in the brain tissue, knowledge has been limited with respect to the existence of tissue resident lymphocytic populations including NK cells. Conventionally, the CNS was known as an immune privileged site with low penetrability of immune cells. However, recent studies have demonstrated the existence of an important inflammatory response to infection in the CNS. Studies of NK cell recruitment into the brain in pathological conditions such as multiple sclerosis and viral encephalitis have led to important but limited information to understand the role of NK cells in such compartment. The aim of the Tick ThaNK project is to generate knowledge that will provide new insights into innate immunity responses executed by NK cells that could lead to novel strategies to improve treatments for infectious diseases.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз