Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New research shows how disease-causing parasite gets around human innate immunity

31.08.2010
Trypanosomes are parasites responsible for many human and animal diseases, primarily in tropical climates. One disease these parasites cause, African sleeping sickness, results from the bite of infected tsetse flies, putting over 60 million Africans at risk in 36 sub-Saharan countries. The recent 1998-2001 sleeping sickness epidemics in South Sudan, Angola, Democratic Republic of Congo and Uganda killed tens of thousands of people and resulted in over a half million infected individuals.

A team of researchers at the University of Georgia and Glasgow University has now shown, for the first time, just how one species of these parasites evades the human innate defenses. The finding could open the way for new classes of drugs and more in-depth studies about how parasites manage to kill so many and cost governments billions of dollars to fight.

"We believe this research represents a paradigm shift and causes us to think more broadly about how pathogens avoid host defense mechanisms," said Stephen Hajduk, professor and head of the department of biochemistry and molecular biology at UGA and one of the leaders of the research. "It turns out that African trypanosomes have evolved a diversity of ways to avoid human innate and acquired immune systems."

The research, published today in the Proceedings of the National Academy of Sciences, was a joint effort between UGA and a group led by Annette Macleod at the University of Glasgow in Scotland. Other authors of the paper include Rudo Kieft, a research professional in Hajduk's lab at UGA; Paul Capewell and Nicola Veitch in the Macleod lab in Wellcome Center for Molecular Parasitology in Glasgow; and Michael Turner of the Biomedical Research Center at the University of Glasgow. The department of biochemistry and molecular biology at UGA is part of the Franklin College of Arts and Sciences. Hajduk also is a member of the Center for Tropical and Emerging Global Diseases at UGA.

The need for a clearer understanding of how these parasites evade human immune systems is at the heart of a serious public health problem, Hajduk said. During the recent epidemics of African sleeping sickness, as many as half the occupants in some African villages were infected with trypanosomes. The geographical isolation of these villages and ongoing civil wars contributed to what many believe were the worst epidemics of sleeping sickness in five decades.

This led to the realization that many of the existing therapies now available to fight African sleeping sickness are often ineffective and have extreme toxicity, frequently causing death. Additionally, there is increasing evidence that while new therapeutics may cure the disease, long-lasting neurological damage can be caused by infection.

The World Health Organization reports that the recent introduction of aggressive population screening in rural areas and distribution of more effective drugs has dramatically reduced the number of deaths, however.

Several species of African trypanosomes infect non-primate mammals and cause important veterinary disease yet are unable to infect humans. The trypanosomes that cause human disease, Trypanosoma brucei gambiense and T. b. rhodensiense, have evolved mechanisms to avoid the native human defense molecules in the circulatory system that kill the parasites that cause animal disease.

Two of the major challenges faced by scientists studying human sleeping sickness have been the identification of the naturally occurring human defense molecules that are active against the trypanosomes causing animal disease, and the identification of the strategies used by the human sleeping sickness parasites to avoid the action of these molecules.

Human innate immunity against most African trypanosomes is mediated by a subclass of HDL (high density lipoprotein, which people know from blood tests as "good cholesterol") called trypanosome lytic factor-1, or TLF-1. This minor subclass of human HDL further contains two proteins, apolipoprotein L-1 and haptoglobin-related protein, which are only found in primates. These proteins work together, in the lipid environment of the HDL particle, as a specific and highly active toxin against the trypanosomes that infect non-primate mammals. Despite its activity against some African trypanosomes, the toxin is completely nontoxic to the human sleeping sickness parasites.

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 blocking the uptake of a nutrient, but still the strategy works and the parasite can infect humans. Now that researchers know how the parasite survives, this may provide an intervention target that could keep the parasites from evading the human defense system. The result could be a newly strengthened innate defense system that halts the parasites in their paths.

The research was supported by grants from the National Institutes of Health and the Burroughs-Wellcome Fund.

Stephen Hajduk | EurekAlert!
Further information:
http://www.uga.edu

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>