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 Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>