1721). The authors find that all three components of a human high density cholesterol complex are needed to kill disease-causing trypanosomes.
Trypanosomes cannot synthesize their own fats, so they feed on the host's portion, which in humans and some other primates includes a cholesterol complex known as the trypanosome lytic factor (TLF). Because TLF is toxic to parasites that lack a specific resistance gene, it acts as a Trojan horse that kills the bug from within. Of the three lipoproteins in TLF, only apolipoprotein (apoL)-1 has been credited for TLF's killing power, via its ability to drill pores into the parasite's membrane that cause the invader to swell and burst.
The group's initial results supported the single-fat toxicity idea; mice engineered to produce only the apoL-1 component of TLF survived otherwise lethal infections. But when plasma from these mice was transferred into normal infected mice, the recipients did not completely clear the parasite; animals that were infused with plasma containing all three TLF components did.
Mouse plasma that contained only apoL-1 had 10% of the lytic activity of whole human plasma. The authors speculate that this feeble but detectable killing capacity might be due to apoL-1's association with endogenous mouse lipoproteins that are similar to other TLF elements.
The other two TLF components might enhance killing by increasing the uptake of apoL-1 by the parasite. One is thought to be a ligand for the parasite's fat-binding receptor, and the other might direct the delivery of the complex to the lysosome, whose acidic environment helps activate apoL-1.
Some trypanosome varieties have a resistance protein that hook to apoL-1's C terminus, which has led to the idea that a version of apoL-1 lacking this domain might provide broad resistance to the parasites. But the authors now dismiss this idea, as mice that expressed the truncated lipid were still susceptible.