The parasite that causes fast-onset, acute sleeping sickness in humans, T. b. rhodensiense, is able to cause disease because it has evolved an inhibitor of TLF-1 called Serum Resistance Associated (SRA) protein. Another species, T. b. gambiense, causes slow onset, chronic sleeping sickness and is responsible for over 95 percent of the human deaths caused by these parasites. Until the just-published research by Hajduk, Macleod and their colleagues, nothing was known about TLF-1 resistance in T. b. gambiense. Hajduk and Macleod report, for the first time, that T. b. gambiense resistance to TLF-1 is caused by a marked reduction of TLF-1 uptake by the parasite.
So how is this happening?
To survive in the bloodstream of humans, these parasites have apparently evolved mutations in the gene encoding a surface protein receptor. These mutations result in a receptor with decreased TLF-1 binding, leading to reduced uptake and thus allow the parasites to avoid the toxicity of TLF-1.
"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," said Hajduk, "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."
The parasite may pay a price for block
|Contact: Stephen Hajduk|
University of Georgia