At first glance, tuberculosis and Parkinson's disease are about as different as diseases get, but a new study has found an important link between the two.
This connection is down to a protein called leucine-rich repeat kinase 2 (LRRK2), and not only could it help develop new treatments for both diseases, but it also demonstrates a key connection between the brain and our immune system.
Parkinson's disease is a neurodegenerative disorder that develops as nerve cells in the brain die, depriving the tissue of a key chemical messenger called dopamine.
Exactly what causes these cells to die in some people is a mystery, though an increasing number of signs point to a confused immune system.
Mutations in LRRK2 have also been implicated in the development of Parkinson's, a find that is already helping scientists who are developing a new class of treatments.
And research led by a team from the Francis Crick Institute and Newcastle University in the UK has now explained how LRRK2 interferes with one of the processes white blood cells use to kill bacteria.
This is where tuberculosis (TB) comes in, because it's an infection caused by the bacterium Mycobacterium tuberculosis, usually within lung tissue.
In most cases, our bodies do a fairly good job of dealing with the infection by sending in white blood cells called macrophages - they swallow the microbes and pack them inside bubbles called phagosomes.
Once the germs are safely trapped inside these compartments, packets of enzymes called lysosomes click into place and empty their bacteria-dissolving contents, killing the infection.
Broad studies of the human genome have hinted at some kind of relationship between inflammation caused by Mycobacterium diseases – including TB and leprosy – and the LRRK2 gene.
What's been missing are the details; just how does a gene connected to Parkinson's disease mess with the way white blood cells deal with mycobacteria?
To get a better idea of what was going on at a cellular level, the team developed several experiments that exposed the chemical's functions.
It turns out that LRRK2 regulates a process that connects those bacterial jail cells with their horror-show bubbles of death, effectively preventing them from joining. Meanwhile, macrophages that were engineered to have LRRK2 missing had no problem digesting their TB captives.
Not only does this discovery shed light on how TB and leprosy infections might get a foothold, but it could also explain why certain proteins accumulate inside nerves.
"We think that this mechanism might also be at play in Parkinson's disease, where abnormal masses of protein called 'Lewy bodies' build up in neurons in the brain and cause damage," says one of report's first authors, Susanne Herbst from the Francis Crick Institute.
This makes the find a two-for-the-price-of-one deal, and the findings could potentially lead to new ways of dealing with Parkinson's - since researchers don't normally think about it in immunology terms.
"The dogma in the Parkinson's field has been to focus almost exclusively on what is happening to neurons in the brain to make them degenerate," says biochemist Patrick Lewis from the University of Reading.
"This study reinforces why we should think more broadly about the events that cause neurodegeneration, and that some of the answers to Parkinson's disease might come from immunology."
Our global society is an aging one, and with that comes an increasing number of neurodegenerative conditions such as Parkinson's. We're going to need all the help we can get in keeping those numbers low.
As for tuberculosis, the timing also couldn't be better. A lengthy course of antibiotics is usually enough to clear up an infection, but the disease still manages to kill more than a million people each year.
In recent years, strains of TB Mycobacterium have emerged that show resistance to one or more of the medications commonly used to treat it. That means the writing's on the wall for a possible resurgence of this deadly disease, one that could prove difficult to control without new classes of drugs.
Knowing more about potential weak points in our own immune system is looking critical, which makes research drawing links between such disparate diseases all the more valuable.
This research was published in The EMBO Journal.