Michael Kimber, Iowa State University
Kat - You may never have heard of the disease lymphatic filariasis, but it affects 120 million people in 70 countries around the world, causing dramatic swelling of the limbs and other parts of the body, known as elephantiasis. Itís caused by tiny parasitic worms, transmitted between people by mosquito bites, which can lie low in the body for many years, hiding from the immune system. But how do they do that? Michael Kimber from Iowa State University has been finding out.
Michael - People have kind of looked previously at various secretions, things that the parasites release whilst they're inside the host, but up to this point, the nature of those secretions, they really haven't given us much of an indication as to how these parasites manipulate people in order to cause the disease that they do. What we wanted to do is to take a more detailed look at that interaction.
Kat - What did you do to study this in more detail?
Michael - Recently, there has been a really invigorated research focus on structures called exosomes. Exosomes are a particular type of small vesicle, extracellular vesicle released by many, many cell types. You can find these exosomes having important functions in things like cancer, other infectious diseases, autoimmune diseases, even neurodegenerative diseases. The consensus seems to be that these exosomes act as cell-to-cell effectors. So, what they do is they carry a cargo that is capable of performing lots of biological function from the cell where itís released to a target cell and then it can manipulate the biology of that target cell.
Kat - So, kind of like a little extracellular postman.
Michael - In many respects, carrying a very dangerous package if you're a host organism, yes.
Kat - How did you go about trying to look for these exosomes in this infection?
Michael - With these parasites, we have the ability to maintain them in vitro. So, we can take them out of the host and keep them alive for a while and study the things that they secrete. So, we maintain some parasites in culture and collected their secretions and profiled them with various techniques.
Kat - What's in them and what are they doing more importantly?
Michael - When we looked at the cargo of the exosomes secreted by these parasites, we found a preponderance of small RNAs called microRNAs.
Kat - These are very interesting arenít they? They are very hot right now.
Michael - Very hot right now. So, they were identified probably 15, 20 years ago, maybe as far back as that. They seem to be agents of genetic change. So, these are small RNA species that humans and other animals, even plants use to control the expression of genes. The identification that parasites secrete microRNAs was interesting because it opens the door to the idea that a parasite is secreting an agent of genetic change and therefore, manipulating gene expression within the host.
Kat - So, the idea would be that these little parcels produced by the parasite are somehow turning genes on and off in human cells. Thatís got pretty big implications for understanding the disease.
Michael - Yeah, I think so. Itís a very intriguing paradigm and certainly, itís a hypothesis that seems to be supported by other studies that are emerging at this time. Other infectious diseases, the same thing is also observed where these pathogens seem to be able to secrete these exosomes containing microRNAs to specifically alter host immune responses and create conditions favourable to the infecting agent.
Kat - Iowa State Universityís Michael Kimber, and that study was published in PLOS Neglected Tropical Diseases.