Trypanosoma are a nasty class of single-celled parasites that cause serious, even fatal, diseases in human and animals. Two species cause sleeping sickness, a disease that threatens all of sub–Saharan Africa. There’s a catch though: one parasite, Trypanosoma brucei brucei (T. b. brucei), infects animals but seems to spare humans, and scientists haven’t quite understood why.
Now, a team of researchers led by biochemists at the University of Georgia propose that T. b. brucei actually does infect humans but that the infection triggers release of hemoglobin from red blood cells. Hemoglobin appears to “arm” the human innate immune system by binding to a small fraction of high density lipoprotein (HDL), or “good cholesterol.” The hemoglobin-HDL complex then becomes a super toxin and clears the body of trypanosomes.
“This is a real paradigm shift in understanding what T. b. brucei does in humans,” said Stephen Hajduk, professor and head of the department of biochemistry and molecular biology at the University of Georgia. “It had always been assumed that it didn’t infect humans at all, but it now appears that it does and that the release of free hemoglobin leads to clearance of the infection. It was incredibly surprising to us.”
Lead author on the research is Justin Widener, a graduate student in Hajduk’s lab. The research was published today in the Public Library of Science Pathogens. Widener is also a student at Brown University, where he began his work with Hajduk, who joined the UGA faculty in 2006. Other authors on the paper include April Shiflett of UGA and Marianne Jensby Nielsen and Søren Krag Moestrup of University of Aarhus in Denmark.
Hajduk and his group are interested in a parasite that does not harm humans because they asked a simple question: why can’t T. b. brucei infect humans although it is nearly identical to the African sleeping sickness-causing parasite" After all, two cousins of T. b. brucei, known as T. b. gambiense and T. b. rhodensiense, cause, respectively, chronic and acute sleeping sickness in humans. The parasites, which are carried by the tsetse fly and injected into humans and animals with its bite, have been a major health issue since the first recorded outbreak of sleeping sickness beginning in 1906.
“We know that humans are protected against T. b. brucei by the action of a high-density lipoprotein called Trypanosome Lytic Factor [TLF],” said Widener. “We investigated the mechanism of how TLF kills the parasite by using a purification technique that allowed us to show that a protein associated with TLF strongly binds hemoglobin and that hemoglobin stimulates TLF to kill the parasite.”
Because all three strains are closely related—T. rhodensiense is different from T. b. brucei by a single gene—what is true for one species could be useful in understanding the others.
While human sleeping sickness has been an important human disease in Africa for more than a century, recent epidemics of the disease in five African nations underscore the potential threat of this disease to travelers and aid workers.
One interesting aspect of trypanosomes is their ability to infect a wide range of mammals, from humans to wild game. The severity of disease caused by T. b. brucei varies depending on the host; infections in humans are cleared while a fatal disease develops in infected cattle. The application of the discovery by Widener on the mechanism of human protection may lead to better treatment of cattle infections by these parasites.
The value of the new research may lie as much in its potential as a model system for studying all trypanosomes as it does in specifically understanding why T. b. brucei doesn’t infect humans.
Kim Osborne | EurekAlert!
A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
20.08.2018 | Information Technology
20.08.2018 | Life Sciences
20.08.2018 | Information Technology