Unravelling the complexities of the brain – one immune cell at a time

Professor Paul McMenamin

The brain is literally the last frontier for the human immune system – for the most part the brain and the immune system remain separate. Increasingly, however, we are learning new ways in which the immune system interacts with the brain, causing diseases such as multiple sclerosis.

A paper from the Biomedicine Discovery Institute’s Professor Paul McMenamin, published in the journal Glia, provides clues to the types of immune cells that are present, and absent, in the brain.

T cells – which mediate chronic inflammatory processes – are generally unwelcome in the healthy brain because the consequences of inflammation such as swelling can be deadly. When these cells do infiltrate the brain, such as in Multiple Sclerosis, they can for example damage the protective myelin sheath that encases nerve fiber tracts in the brain and spinal cord.

Almost a decade ago scientists from the Rockefeller Institute in New York published research that detailed the presence of dendritic cells, the sentinel cells of the immune system that direct T cells in recognizing ‘self’ and ‘non-self’, in the healthy mouse brain. The implications of this finding was that these pivotal immune cells were always present in the normal brain and are not necessarily associated with disease states. This flew in the face of many previous decades of research but became generally accepted.

In the Glia paper, Professor McMenamin and his team dispute these studies from 2008 that claimed there are dendritic cells in the mouse brain.

McMenamin and his post-doctoral fellow, Dr Samantha Dando, undertook highly accurate dissections of the mouse brain to identify the exact location of these dendritic cells. They found that these dendritic cells were actually contamination of brain tissue from the “outer” coverings or meninges of the brain (dura, archanoid and pia mater) and from the choroid plexus within the ventricles of the brain. It has been long known that these sites contain immune cells. “It’s likely that original research showing the presence of dendritic cells in the brain was due to residues of dura and pia etc contaminating the samples” Professor McMenamin said.

Importantly Professor McMenamin believes that there are cells within the brain – called microglia – which “while looking a lot like dendritic cells they are simply macrophages masquerading as dendritic cells” he said.