Gut Education of Brain Immune Cells

Immunoglobulin Alpha (IgA) Antibodies are educated in the gut before providing protection in the brain.

Lethal infectious diseases are constantly plaguing the membranes surrounding the human brain. This is because microbes are in a never ending struggle to evade the immune cells and glide past the meninges a special protective layer of the brain. One study evaluating mice and tissue from human autopsy, noted that these immune cells are gain their resilience against infections after learning to fight infections in the gut.

This is novel in the field of neuroimmunology. This study identified that antibody producing cells haven spent time in the gut, now defend regions that surround the central nervous system (CNS).

Naturally, the meninges a three-layered membrane protects the CNS from disease causing microorganisms (pathogens). Additional protective systems include specialized tightly sealed blood vessels. The outermost layer of the meninges, the dura mater, lacks this specialized tightly sealed blood vessels and contain sinuses large venous structures that transport blood at low pressure back to the heart. A combination of slow blood flow and proximity to the brain is required to institute strong immune protection to prevent potential infections. The venous sinuses within the dura mater act like drainage bins, therefore harboring pathogenic microorganisms that can enter the brain. In other to prevent this, the immune system ought to create a barrier in within the sinuses. A major discovery of this study was that, in the meninges of mice and humans several immune cells present, were formally trained to make antibodies targeted at specific microbes. IgA cells typically found in barriers such as the mucous membranes of the bronchial tree of the lungs and gut are also a major constituent of the dura mater. This was confirmed, by comparing the results obtained with those in mice lacking their own microbiome, it was found that, Mice in the control group lacked IgA in their meninges. The microbes were introduced into the guts of mice, the development of IgA was observed, this did not occur when the skin of germ-free mice was reconstituted with different microbes, suggesting that bacteria in the gut were important in educating meningeal IgA cells. In other to confirm that the cells in the meninges originated from the gut, the DNA sequences of IgA cells were studied. Possibly IgA sequences vary throughout the body, this makes their abilities to detect pathogens more diverse, therefore if two sequences are similar, it means that they both originated from the same source. This was the case when the sequence of IgA taken from the meninges were compared with those taken from the gut, the overlap was more than 20 percent. This was a clear indicator that immune cells protecting the brain had been educated in the gut. The lining of the gut is also sealed to prevent leakage of its content. Inflammation and activation of the immune system occurs when the gut is injured physically, to test this, the researchers breached the gut and observed a defense response similar to that in the meninges, immune cells defending against the presence of microbes in the blood. The response of IgA in infection was proven to be of utmost importance when pathogenic fluorescent fungi was introduced into mice with low or absent IgA antibodies, the response was infection of the brain by this fungus, which would have been prevented in the presence of IGA. It was also noted that antibody secreting cells ensure constant supply of antibodies as a preventive measure against impending attack. This is the measure means of immune response in the meninges. In conclusion, it was confirmed that, IgA antibodies present in the meninges decrease in number when mice were treated with antibiotics and similarly changes in microbiome affects the ability of the immune cells to respond to infection. Future focus is on mechanisms that allow for continual education and re-education of IgA cells in the meninges.

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