A new study at University of Liverpool has investigated the derogatory role of immune system in chronic brain infection caused by cold sore virus. Researchers determined a specific type of immune cells, that under aberrated conditions, induce brain inflammation in herpes simplex virus (HSV) encephalitis.
Importantly, specific protein that signals the immune cells and carries them to transfer into the brain from blood, are also identified. These revelations can significantly help in developments of targeted treatment to control inflammation inducting immune cells to prevent brain infection, the most common global cause of viral encephalitis. Study findings are published in the Cell Reports.
Key Role of Immune Cells in Brain Infection Identified
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Over exuberant immune response has predisposed to significant proportion of morbidity in US due to Herpes simplex virus (HSV) encephalitis, where over-active immune response is characterized by immune cells infiltrating into the brain. It is an illness affecting both general and focused brain functions resulting in brain infections, believed to occur by direct neuronal transmission of the virus from brain and decreased the permeability of blood-brain barrier, a complex network of blood vessels and tissue made up of closely spaced cells, that keeps harmful toxic substances and pathogens from reaching the brain.
Virus spreads profoundly and despite rapid anti-viral drug treatment most people die. Those who survive are left with brain injury due to the inflammation and by the virus. Moreover, one third of HSV cases are prevalent in children and adolescents. Common signs and symptoms include headache and fever for a few days, followed by confusion, focal deficits, seizures or hemiparesis, hallucinations, and altered levels of consciousness.
Researchers used a mouse model and demonstrated that a specific immune cell called neutrophils increase the permeability of the blood-brain barrier, compromising its selectiveness, leading to brain damage associated with HSV encephalitis. Further, it was revealed that these neutrophils were not crucial to control the virus. Alongside, another type of immune cells called monocytes, which when matured to macrophages, play significant role in controlling inflammation. Therefore, it is proposed that these cells could be used to prevent brain damage by controlling the virus.
Further, researchers identified the exact signaling protein, called CXCL1, it acts as a carrier that aids the migration of these damaging neutrophils into the brain during HSV infection. In mouse model, blockage of the proteins significantly reduced the inflammation and improved the blood-brain barrier permeability. Therefore, this protein can be used as a potential therapeutic target to develop future targeted therapeutic treatments.
“There is currently no licensed treatment for the severe brain swelling which occurs despite antiviral therapy in HSV encephalitis. Sometimes steroids are given, but as these suppress the immune system in a very broad way, there is a risk of uncontrolled viral infection. There is an urgent need for targeted treatment that prevents damaging immune cells from entering the brain without limiting the immune cells needed to control the virus,” Dr Benedict Michael, a Senior Clinician Scientist Fellow at the University of Liverpool.