New Approach to the Treatment of Viral Encephalids

Unusual virus defense in the brain decoded

viral encephalids
PM_chhatbar_590x240.jpgDr. Chintan Chhatbar © TWINCORE

Our brain is one of the best protected areas of our body. Among other things, the blood-brain barrier providesensuring that only selected substances from our bloodstream can pass into the central nervous system and shields our brain from pathogens, toxins and messengers. Like any security system, that of the brain also has vulnerabilities. A void that viruses such as influenza, FSME, dengue or herpes viruses use is our sense of smell. If the viruses succeed in overcoming this barrier, the brain becomes inflamed: a life-threatening encephalitis can develop. Scientists at TWINCORE have now decoded a very specific immune response of the brain, which is based on completely different mechanisms, as the pathogen defense in the rest of our body. Their results are now published in the journal Cell Reports.

“Actually, we have assumed that the first defense reaction of the immune system in the brain runs for similar patterns, as in the rest of the body, even if the immune systems through the blood-brain barrierimmune cells register the invading virus and initiate further defense via interferon signals, “says Dr. Chintan Chhatbar, junior scientist at the Institute for Experimental Infection Research. “We have studied these processes more closely to better understand how a protective immune response works in the brain. “Even if patients successfully recover from encephalitis, patients often suffer from personality changes, epilepsy, or motor disorders. The question the team asks at TWINCORE is: how can patients best be helped with viral encephalitis – without harming the brain?

The path of the virus leads via the olfactory nerve directly into the brain. The individual olfactory fibers of the nerve run through a perforated bone plate of the skull – the so-called mesh plate – to the olfactory bulb. It sends the incoming signals to the brain for processing, and it is there that the brain’s first defense reaction against the virus takes place: Interferon is produced to intercept the viruses that have migrated up the olfactory nerve. But who triggers this interferon production and who processes the information? “With imaging we can directly track what happens during an infectionwith the vesicular stomatitis virus (VSV) – our model virus – happens in brain structures, “explains Chintan Chhatbar. In the central nervous system, four cell types are particularly important: microglial cells, guard and clearing command of the brain; Astrocytes, assistant group of electrically excitable structures of the brain; Oligodendrocytes, isolation and filling station of the nerve tracts and of course the most diverse neurons, the computing units of our supercomputer. After the infection with the VSV, the immune cells of the brain, the microglial cells, first began to multiply in the wider environment of the olfactory bulb and then to the focal point of infectionto migrate to eliminate the viruses. On the other hand, if the researchers remove the microglial cells, the virus has a clear path and the brain can not defend itself against the infection .

In order to better understand the signal chain that leads to this microglial activation and migration, the team at TWINCORE analyzes in particular the central information unit of the immune system: the messenger substance interferon. Interferon is released by the cells that detect the virus during each viral attack. They alert all other cells and the defense reaction takes its course. “We have each switched off the interferon receptors of the microglial cells, astrocytes or neurons so that they can no longer register interferon,” says Chintan Chhatbar. “What we saw was amazing: microglial cells do not care if they can detect interferon or not – they migrate and defend the virus in any case. But if astrocytes or neurons no longer have interferon receptors, The microglial cells do not react either. They neither multiply nor migrateThe focus of infection . “Apparently, these two cell types form specific messengers, after they have perceived the interferon signal, which in turn stimulate the microglial cells to propagate and migrate. A very complex and thus very secure mechanism, because all three cell types have to interact with each other to activate the microglial cells.

“We do not yet know which messengers are,” says Prof. Ulrich Kalinke, director of the Institute of Experimental Infection Research, “but in the pathway lies the key with which we can help the brain viral infections. Hopefully, this will provide a strategy for developing new therapies for viral encephalids that support brain healing without harming it. ”

Source : Helmholtz Center for Infection Research GmbH