Disfiguring disease caused by alliance between 3 parasites

The patient’s nose looks like it has melted away. Several years ago, she noticed an unsightly ulcer on her face. It eventually healed, but it returned with reinforcements. Together, the onslaught of ulcers slowly ate away at the tissue round her nose and mouth.

Her condition is known as mucocutaneous leishmaniasis, or espundia. It’s the result of a combined assault from three different parasites, separated by billions of years of evolution and united in their disfigurement of this woman’s face.

The first partner is a sandfly. Through its bite, this blood-sucking insect spreads the ringleader of the infectious trio – a single-celled protozoan called Leishmania guyanensis (which gives the disease its name). Once inside the skin, Leishmania takes down our immune system from within. It gets sucked up by white blood cells but instead of being digested, it converts the cells into factories for producing more Leishmania. In doing so, it triggers an intense wave of swelling and inflammation – this is what causes the disfiguring ulcers.

But Leishmania doesn’t work alone. Annette Ives from the University of Lausanne has found that it uses a virus called LRV-1 to usurp the host’s immune system.

Only 5-10% of people infected with Leishmania go on to develop disfiguring ulcers. When Ives looked at the parasites responsible for the worst symptoms, she found that they were loaded with LRV-1, or Leishmania RNA virus-1 in full.

Paradoxically, the virus actually helps the parasite by triggering the host’s immune defences. Its outer shell is made of molecules that are recognised by a host protein called TLR3. This sentinel alerts white blood cells to the presence of foreign molecules. When it detects the virus, it raises the alarm and the cells starts pumping out chemicals that trigger inflammation.

This is all part of our normal response to infections. It normally helps, but in the case of Leishmania, it makes things worse because the swollen tissues provide a safe refuge for the parasite. When Ives studied infected mice, she found that those with the strongest immune responses were actually more vulnerable to infections, and suffered from the worst symptoms. If the mice lacked TLR3 entirely, they were better at resisting Leishmania and their symptoms were milder.

Ives thinks that after the immune system fights off an initial Leishmania assault, the dead parasites release their viruses and create the ideal conditions for later infections. This could explain why the first espundia ulcer usually heals, only to return in force later.

Ives’s discovery is promising. It means that doctors could work out which patients run the greatest risk of disfiguring lesions by searching for the LRV1 virus. It also means that the disease could be treated more effectively with a combination of drugs that target both Leishmania and its viral accomplice.

This isn’t an isolated example. The slideshow below describes four other parasite alliances, all involving viruses.

Reference: Ives et al. Leishmania RNA Virus Controls the Severity of Mucocutaneous Leishmaniasis Science http://dx.doi.org/10.1126/science.1199326

Image by Zephyris (depicts a different species of Leishmania