Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chagas’ disease: virulence factor identified

07.01.2004


Chagas’ disease affects over 18 million people in Latin America. The agent responsible is a protozoan parasite, Trypanosoma cruzi, transmitted by haematophagous insects. For survival in the host’s organism, it uses several strategies, but especially one of inhibiting the host’s immune response. Research scientists from the IRD and INSERM (1) who are studying this trypanosome found that one of the proteins it secretes, Tc52, is a virulence factor that plays a pivotal role in the infection mechanism. Combining different in–vitro and in-vivo approaches, they brought into evidence its role in the development of infection and performed the molecular characterization by peptide analysis of the minimal sequence of Tc52 that carries immunosuppressive activity. Knowledge of the biological activity of this factor raises the prospects for developing vaccination strategies or drugs to combat T. cruzi.



Chagas’ disease – or American trypanosomiasis – is a parasitic illness which affects nearly 20 million people mainly in tropical regions of Central and South America. The aetiological agent that causes it is a flagellate protozoan, Trypanosoma cruzi, transmitted to humans by haematophagous insects (Reduviidae). Research scientists from the IRD research unit "Pathogénie des Trypanosomatidae" and co-workers from INSERM have studied the parasite’s development cycle, its virulence and its involvement in the infection process, with a view to identifying possible prevention and control methods. Using techniques of cellular and molecular biology, and of biochemistry, they sought to identify the nature and function of T. cruzi genes which code for the factors responsible for the virulence, in particular a protein called Tc52.

As in any parasitic disease, the pathogen’s ability to survive in its vertebrate host depends on many mechanisms, especially one which weakens the host’s immune response. In Chagas’ disease, during its life-cycle in humans T. cruzi takes on two forms, an infective flagellate one (trypomastigote) which circulates and reproduces in the blood and another intracellular one without flagellum (amastigote), which in its turn multiplies to produce another batch of circulating forms. These two forms prove to be able to secrete this protein Tc52. The research team revealed it to have several activities, including enzyme activity (2) and an immunosuppressive activity. The protein released by T. cruzi influences in a complex way the physiology of the host cell. It acts on cells of the immune system, the macrophages and the dendritic cells, and notably blocks the production of interleukin 2 (IL-2), a cytokine necessary for T-lymphocyte proliferation, in this way exerting an immunosuppressive activity.


Experimental infections with T. cruzi have been conducted in the laboratory on mice immunized beforehand with this protein. These led to a reduction in mortality rate during the acute phase of the disease, showing that it is possible to protect them partially against such infection. In addition, mutant parasites obtained by targeted deletion of a protein-coding allele of the Tc52 gene have been used for analysis, again in vivo, of the effects of a decrease in Tc52 production on the host immune response and the development of symptoms of the chronic phase, especially the inflammation reaction. Infection by these mutants results in normal production of IL-2 and attenuation of these symptoms. The research team subsequently performed the molecular characterization of the minimal amino-acid sequence, or minimum functional domain, of the protein responsible for the immunosuppressive activity.

The results of this work as a whole demonstrate that this protein secreted by T. cruzi plays a key role in the development of the infection and the pathological manifestations of Chagas’ disease. As its enzyme and immunosuppressive activity are now known, the prospect emerges of developing biochemical strategies– involving inhibition of Tc52’s enzyme activity by anti-parasitic drugs – or vaccines, against T. cruzi. Research projects are currently planned in conjunction with other institutes (3) with the objective of molecular characterization of particular receptors of this protein situated on the macrophages and the dendritic cells, and of devising specific inhibitors. In this way they will contribute to formulation of the tools necessary for drug development.

(1) UR 008 Pathogénie des Trypanosomatidae of the IRD
(2) thioltransferase, involved in the parasite’s protection against oxidation stress.
(3) CNRS Laboratoire d’immunologie et chimie thérapeutique (UPR 9021) at Strasbourg and INSERM joint research unit (UMR) 564 of Angers Faculty of Medicine.


References:

Borges M, cordeiro-Da-Silva A, Sereno D & Ouaissi A. Peptide-based analysis of the amino acid sequence important to the immunoregulatory function of Trypansosma cruzi Tc52 virulence factor. Immunology, 2003, 109: 147-155.

Garzon E, Borges M, Cordeiro-Da-Silva, Nacife V, Nazareth M, Guilvard E, bosseno MF, guevara A, Breniere FS & Ouaissi A. Trypanosma cruzi carrying a targeted deletion of a Tc52 protein-encoding allele elicits attenuated Chagas’disease in mice. Immunol. Lett., 2003, 89: 67-80.

Borges Margarida – Molecular and functional characterization of Tc52 virulent factor properties from Trypanosoma cruzi: analysis of its role in immunopathological processes observed during infection. Thesis upheld on 6/10/2003 at the University of Porto, Portugal.

Bénédicte Robert | EurekAlert!
Further information:
http://www.paris.ird.fr/

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>