Study suggests 'sleeping sickness' parasite mutated to evade immune system defences

Wednesday, September 1, 2010

File photo of trypanosoma brucei

Research teams from the universities of Georgia and Glasgow discovered the mechanism the Trypanosome parasite evolved for "sleeping sickness" disease to circumvent the human immune system. Their study follows a recent African outbreak of the disease this parasite causes. The discovery is expected to help develop a cure preventing future deaths.

A tsetse fly, generally responsible for the spread of the condition.

The 1998–2001 sleeping sickness epidemics in South Sudan, Angola, Democratic Republic of Congo, and Uganda caused tens of thousands of deaths. The parasites are spread by tsetse flies. It is considered one of the worst epidemics in the last five decades. As WHO reported, subsequent recent introduction of population screening in rural areas and distribution of more effective drugs had potentially reduced the number of death incidents. However, the main effect of these measures being a decrease in spreading of the parasite and not in decrease of the death rate, the researchers decided to tackle the puzzle.

The scientists studied the molecules the human immune system activates in response to the attack. They were looking for the way the parasites inhibit it and lead to the death of the victim. Of the several known parasite species, the two that can infect humans were chosen to study, called Trypanosoma brucei gambiense and Trypanosoma brucei rhodensiense. Several others also exist, but they affect only animals.

Researchers knew that the Trypanosoma attacks typically are repelled by an HDL, more specifically trypanosome lytic factor-1 (TLF-1). It is generated in the humans' immune system and is toxic to the parasites but not to humans. It was known that one of the parasites, T. b. rhodensiense, has evolved an inhibitor of the toxic chemical, called Serum Resistance Associated (SRA) protein. However the other one, T. b. gambiense, was responsible for over 95% of human deaths, and it had been previously unknown why.

The study showed that a gene mutation has lead to a change in the parasite's surface protein receptor. It doesn't bind to TLF-1 as well as for other species, leading to a substantial decrease in TLF-1 uptake by the parasite. The receptor is more strict, causing a lower nutrient intake as well, but it suffices, and the parasite defends against the human immune system.

As professor and head of the department of biochemistry and molecular biology at UGA (and one of the leaders of the research) Stephen Hajduk explained, "Humans have evolved TLF-1 as a highly specific toxin against African trypanosomes by tricking the parasite into taking up this HDL because it resembles a nutrient the parasite needs for survival. But T. b. gambiense has evolved a counter measure to these human 'Trojan horses' simply by barring the door and not allowing TLF-1 to enter the cell, effectively blocking human innate immunity and leading to infection and ultimately disease."

Based on the results of the research, humans could possibly develop a defense mechanism to keep the parasites from evading the human defense system. Stephen Hajduk commented, "We believe this research represents a paradigm shift and causes us to think more broadly about how pathogens avoid host defense mechanisms. It turns out that African trypanosomes have evolved a diversity of ways to avoid human innate and acquired immune systems."