The immune system is comprised of two separate responses referred to as either innate or adaptive immunity. Both work in collaboration to elicit protection against anything the body encounters as ‘foreign’. In many cases foreign pathogens that enter the body are recognized by the innate immune system first which then activate adaptive immunity. The innate immune system uses many broad, non-specific cells to detect anything that might cause harm to the body. These cells initiate inflammation and the overall immune response. The adaptive immune system comes second and is more specific to the invading pathogen. Adaptive immune cells can not only help lyse or kill the invaders, but also generate cells to ‘remember’ that pathogen in the future. This is a common phenomenon that occurs when we overcome an illness and is known as immunological memory. Vaccine biology is based on this concept that we will generate ‘memory cells’ in response to attenuated viruses.
The study of immunity and how our body fights off disease is a progressively growing field. Currently, scientists know many of the key players that drive this immunological memory. However, researchers and physicians are working together to better understand this process and how to generate more effective treatments for various diseases. An exciting article in Nature, published by Dr. Francisco J. Quintana and others, demonstrate that a glial cell can generate immunological memory. Quintana, an investigator at Brigham and Women’s Hospital, and his team study different signaling pathways associated with immune activity to identify novel therapeutic treatments and biomarkers to measure treatment efficacy. The glial cell Quintana and his team found to aid in immunity is known as an astrocyte, which is a key cell within the central nervous system (CNS). Astrocytes help promote synapse formation, clear excess neurotransmitters, and maintain the blood-brain barrier.
For the first time astrocytes have been connected to obtain memory-like properties and aid in immunity. The team used multiple models to demonstrate that astrocytes can remember previous interactions with immune cells. Not only did this function improve response time to infection but induced a stronger immune response when re-exposed to the same disease. Due to similarities in memory formation, Quintana and others refer to this process as ‘astrocyte immune memory’. Interestingly, due to astrocytes long lifespan, these cells could provide insight into chronic neurologic disorders.
The investigators discovered that the gene expression within these memory-like astrocytes was altered and that the intracellular program was driven by two genes: p300 and ATP-citrate lyase (ACLY). Importantly, these two genes were upregulated in mouse models that had a chronic disorder, multiple sclerosis (MS). When these genes were downregulated in memory-like astrocytes, CNS inflammation and disease progression was reduced. Similarly, highly expressed p300 and ACLY in astrocytes in chronic MS human samples.
The discovery of memory-like astrocytes is a foundational finding that helps improve our knowledge of the nervous and immune system. More importantly, it demonstrates the interaction between the two and how our bodies react to chronic neurological disorders. The work done by Quintana and others provide insight into the function of astrocytes in disease, but also how these cells promote MS. As a result, scientists and physicians can develop treatments to improve quality of life in patients and even work towards a cure for neurological disorders.
Article, Nature, Francisco J. Quintana, Brigham and Women’s Hospital
