Immune cells in the brain make a sentinel against virus invasion

FThe smell of diapers containing freshly cut grass and poop is a potential sign of COVID-19 infection, at least recently. “People say things smell strange or can’t smell at all,” says Harvard neurobiologist Sandeep Datta. Datta read about people’s experience of olfactory dysfunction and wondered how SARS-CoV-2, the virus that causes COVID-19, has this effect. One possibility was that the virus would attack the cells that line and support the olfactory neurons in the nose. Alternatively, SARS-CoV-2 may be directly targeting the neuron itself.

The work of Datta and other researchers — so far genetically And Cellular Analysis of humans, rodents, and monkeys suggests that mammalian olfactory neurons do not have suitable cell receptors for the virus to invade. This means that the lack of olfaction is most likely due to an infection of olfactory supporting cells. But not everyone is convinced by the data. Some researchers continue to argue that SARS-CoV-2 can infect neurons in the nose and eventually invade the brain in this way.

Microglia swallowed some of the virus from infected neurons in the olfactory bulb.

If the virus could invade olfactory neurons, it would theoretically be a “very short pathway” along a single neuron from the nose to the brain, said Debbie Van Riel, a pathologist at the Erasmus Medical Center in the Netherlands. Stated. Van Riel, who began studying the ability of influenza to attack nerve fibers involved in the sense of smell decades ago, says he is not convinced that SARS-CoV-2 can infect olfactory neurons. But this discussion reminded scientists of little knowledge about the invasion of the virus through the nose. As a result, she says she was fascinated by reading a recent experiment by Duke University immunologist Ashley Moseman and colleagues who tracked the immune response of mice with vesicular stomatitis virus (VSV) erupting into the nose.

VSV is known to infect mouse olfactory neurons. The team was interested in what Morseman called the “sneaky front door” for the virus to move through nerve fibers that stick out of the nasal passages and connect to deeper neurons in the brain. Mice infected with the virus do not die from the infection when they enter the brain and do not cause any serious brain damage. Interested in how mice avoided this damage, Moseman and his colleagues tagged VSV particles with a highlighter and injected them into the mouse’s nose, which infected the immune system. I decided to see if the team could reveal how they responded.

Fluorescence imaging showed that VSV infects nerve fibers in the nose and nerve cells above the olfactory bulb. “VSV gets into neurons in the nose and actually kills them,” said Dorian McGavern, a viral immunologist at the National Institute for Neurological Disorders and Stroke, who co-authored the study. “But those neurons can go back. They can replenish the system and restore the sense of smell.” Neurons above the brain can’t regenerate, but strangely. , Did not appear dead after infection.

Nerve pathway: Six days after infection, the virus (green) appears in nerve fibers protruding into the olfactory bulb (OB) of mice. This means that the virus has spread from the nose to the brain.

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Upon closer examination, Moseman, McGavern, and their colleagues revealed how neurons deeper in the brain escaped. Microglia, the primary immune cells in the brain, swallowed some of the virus from infected neurons in the olfactory bulb. Although microglia did not infect themselves, they projected flag-like pieces of the virus onto the cell surface, attracting killer T cells in the blood to reach the brain. Mount immune defense For microglia, not for infected neurons. These neurons also display virus bits on the surface. The team found that the interaction between microglia and killer T cells triggered the release of cytokines from T cells, which in the process eliminated the virus from infected neurons without killing them. “Microglia play an absolutely important role here in protecting neurons in the brain,” says McGavern.

What is still unclear is whether killer T cells actually kill what is flaunting the virus.
Whether microglia, or two types of immune cells, interact in other ways to spur T cells and release cytokines that eradicate the virus. “Microglia can be a hit on behalf of everyone,” says Morseman. “By doing so, T cells avoid attempting to engage with neurons that do not adequately replenish themselves.” Losing microglia is a nerve, as he speculates that microglia are interchangeable. It may be less important than the irreversible damage of cell death.

Van Riel says the work gives a glimpse of how the body and brain respond to the invasion of viruses such as VSV through the nose. “If the body knows how to deal with an infection without causing serious symptoms [brain] Injury, which can lead to new insights that can lead to treatment strategies. But scientists still don’t quite understand which viruses can invade the central nervous system in this way. It may change as more researchers investigate whether SARS-CoV-2 is possible. This study may suggest that all viruses elicit a unique immune response in the brain, Van Riel said. “I think we’re only looking at the tip of the iceberg.”