Key role of immune cells in brain infection

Date:
September 15, 2020
Source:
University of Liverpool
Summary:
Researchers have identified the specific type of immune cell
that induces brain inflammation in herpes simplex virus (HSV)
encephalitis. Crucially, they have also determined the signalling
protein that calls this immune cell into the brain from the
bloodstream. The findings could aid the development of targeted
treatments for the brain infection, which is the most common cause
of viral encephalitis worldwide.



FULL STORY ==========================================================================
A new study has detailed the damaging role played by the immune system
in a severe brain condition most commonly caused by the cold sore virus.


========================================================================== Researchers have identified the specific type of immune cell that induces
brain inflammation in herpes simplex virus (HSV) encephalitis. Crucially,
they have also determined the signalling protein that calls this immune
cell into the brain from the bloodstream.

The findings, published in Cell Reports, could aid the development of
targeted treatments for the brain infection, which is the most common
cause of viral encephalitis worldwide.

HSV encephalitis takes hold quickly and, despite rapid anti-viral drug treatment, many patients die. Most survivors are left with brain injury
due to the inflammation and damage caused by the virus and immune cells
gaining access to the brain, breaking down the blood-brain barrier.

"Determining the roles of specific immune cells and the factors that
allow them to cross the protective blood-brain barrier is critical
to develop targeted immune-therapies," explains Dr Benedict Michael,
a Senior Clinician Scientist Fellow at the University of Liverpool,
who led the research.

Using a mouse model, the researchers showed that neutrophils (a type of
immune cell) made the blood-brain barrier more permeable and contributed
to the brain damage associated with HSV encephalitis. They also found
that these neutrophils were not needed to control the virus.

Meanwhile, monocyte immune cells were found to play a protective role
and were needed to control the virus and prevent brain damage.

The researchers also identified the exact signalling protein, called
CXCL1, that drove the migration of these damaging neutrophils into the
brain during HSV infection. By blocking this CXCL1 protein, neutrophils
were prevented from crossing the blood-brain barrier and causing
inflammation which resulted in less severe disease.

The findings make the CXCL1 protein an attractive target for new therapies
that can stop the influx of damaging white blood cells without limiting
the roles of protective ones.

Dr Michael said: "There is currently no licenced 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." Now Dr Michael and colleagues are planning
to examine the impact of the CXCL1 signalling protein in patients who
have already had steroids as part of a clinical trial led by Professor
Tom Solomon at the University of Liverpool.


========================================================================== Story Source: Materials provided by University_of_Liverpool. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Benedict D. Michael, Laura Bricio-Moreno, Elizabeth W. Sorensen,
Yoshishige Miyabe, Jeffrey Lian, Tom Solomon, Evelyn A. Kurt-Jones,
Andrew D. Luster. Astrocyte- and Neuron-Derived CXCL1 Drives
Neutrophil Transmigration and Blood-Brain Barrier Permeability
in Viral Encephalitis. Cell Reports, 2020; 32 (11): 108150 DOI:
10.1016/ j.celrep.2020.108150 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915133159.htm

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