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B-lymphocytes as effector white blood cells for immunoregulatory mechanisms during the infection with Trypanosoma cruzi

Elina ZUÑIGA researcher laureate
elinazuniga@hotmail.com

°1972 Argentina
Licence in biochemistry, Universidad Nacional de Córdoba, Argentina, 1995

Linfocito B: Blanco y efector de mecanismos inmunoregulatorios durante la infección con Trypanosoma cruzi

Elina Zúñiga’s doctoral thesis has made a significant contribution to the unravelling of the mechanisms by which Chagas’ disease develops as a chronic infection. Chagas’ disease is a frequent and feared condition in the tropics. It is responsible for the onset of heart problems and damage to specific muscular tissues, and can remain in humans for 20 to 30 years as a chronic infection. There is no effective treatment for this disease as yet. It is caused by the protozoon Trypanosoma cruzi. Infection with this parasite results initially in an enormous stimulation of the host’s immune system: for example, the number of B-cells multiplies greatly. This same enormous B-cell activation is then used by the parasite as a means of constructing its own defence against the destructive effects of the host’s immune system. Dr. Zúñiga has shown in her work that the activated B-cells undergo apoptosis more quickly. Apoptosis implies that active cell death occurs. In other words, enzymatic processes are triggered in the B-cells, which result in the death of the cells. Cell death is normally used by the immune system as a control mechanism for maintaining the immune system in balance: after the activation of lymphocytes as a result of an infection, a phase of ‘normalisation’ follows, during which the number of lymphocytes is reduced again. This study reveals that Trypanosoma itself provides recognition signals which, among others, trigger apoptosis at a point when this is not yet desirable. Because of this, a proportion of the host’s defensive lymphocytes are prematurely switched off, resulting in a weakened immune response. This explains various points, including why the parasite succeeds in gaining a chronic presence in the host. Dr. Zúñiga then investigates in great detail which mechanisms are responsible for the premature apoptosis of the B-cells. One of her most important findings is that Fas/Fas ligand interactions play a key role here. These molecules are presented on the surface of the B-cells after interaction with the parasite. This interaction then causes B-cells to be eliminated. This new information may, as is rightly pointed out by Dr Zúñiga, prove useful in the development of a new treatment. Future research will show whether it is possible to interfere with the Fas/Fas ligand interaction and hence give the host’s immune system more of a chance to build up a defence against Trypanosoma cruzi. This new knowledge, which we owe to Dr Zúñiga, represents just one part of her work, though. For example, Dr Zuniga has also studied other mechanisms which are responsible for apoptosis. Thus it turns out that activated B-cells also produce a beta-galactose binding lectin, and that this lectin has an influence on the action and survival of T-cells and infected macrophagi.
There is, therefore, no doubt that this work has made a significant contribution to efforts to combat Chagas’ disease. The knowledge which has been acquired extends our general basic knowledge of immunology, and will prove useful, particularly in the understanding and tackling of other similar infections, such as malaria and African trypanosomiasis.
 

report by Dr M. Maras, Department of biology, Universiteit Antwerpen, Belgium