Target Health Blog

Microglia in the Olfactory Bulb May Protect the Brain From Infection

June 29, 2020

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Virology
Source:

Neurons in the nose respond to inhaled odors and send this information to a region of the brain referred to as the olfactory bulb. Although the location of nasal neurons and their exposure to the outside environment make them an easy target for infection by airborne viruses, viral respiratory infections rarely make their way from the olfactory bulb to the rest of the brain, where they could cause potentially fatal encephalitis. According to a study published in Science Immunology (5 June 2020), a specific, front-line defense has been identified that limits the infection to the olfactory bulb and protects the neurons of the olfactory bulb from damage due to the infection.

Taking advantage of special viruses that can be tracked with fluorescent microscopy, the authors found that a viral infection that started in the nose was halted right before it could spread from the olfactory bulb to the rest of the central nervous system. Additional experiments showed that microglia, immune cells within the central nervous system, took on an underappreciated role of helping the immune system recognize the virus and did so in a way that limited the damage to neurons themselves. This sparing of neurons is critical, because unlike cells in most other tissues, most neuronal populations do not come back. Because of this, the central nervous system has evolved to include several defense mechanisms designed to keep pathogens out. However, when airborne viruses are inhaled, they travel through the nasal passages and interact with a tissue called the olfactory epithelium, which is responsible for our sense of smell. Neurons at the edge of the olfactory system extend small projections through the bone lining the nasal cavity. These projections enter the brain, giving it access to odors present in the air. Neurons in the olfactory epithelium also offer an easy way for viruses to bypass traditional central nervous system barriers by providing a direct a pathway to the brain.

For the study, the authors were able to show that CD8 T cells, which are part of the immune system responsible for controlling viruses, are very important in protecting the brain after infection of nasal tissue. Using advanced microscopy, the authors watched in real time how CD8 T cells protected the brain from a nasal virus infection. Interestingly, the CD8 T cells did not appear to interact directly with neurons, the predominately infected cell population. They instead engaged microglia, which are central nervous system immune cells that act a bit like garbage collectors by clearing cellular debris and dead cell material. When a viral infection occurs, the microglia appear to take up virus material from the surrounding environment and present it to the immune system as though they had become infected. In this way, infected olfactory neurons can “hand off“ virus particles to microglia, which were then detected by the T cells. The T cells then respond by releasing antiviral molecules that clear the virus from neurons in a way that does not kill the cells. Because microglia are a renewable cell type, this type of interaction makes sense from an evolutionary standpoint.

Considerable attention has been paid to respiratory viral infections of late due to the current COVID-19 pandemic. The authors noted that, while that virus was not studied in these experiments, some of the symptoms it produces suggest that the same mechanism described here could be in play, since one of the interesting symptoms associated with infection by novel coronavirus is that many people lose their sense of smell and taste. The authors added that this suggests that the virus is not only a respiratory pathogen, but likely targets or disrupts olfactory sensory neurons as well.

For more information:

Meningitis and Encephalitis Information Page

Meningitis and Encephalitis Fact Sheet

Source: NIH

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