Analyse van trypanosomiase-geassocieerde inhibitie van B-cel lymphopoiese en mogelijke interventie strategieën. (FWOTM485)

African trypanosomiasis is caused by parasitic infection and is a heavy burden for both social and economic developments in Sub-Saharan Africa. Every year, this disease affects more than 500,000 human victims and involves around 2 million head of cattle, which has fallen by 1 billion a year. Preventive vaccination against trypanosomiasis is being there. Trypanosomes The immune system of the host is avoided by an ingenious system of area-protein variation. The surface of An African trypanosome is covered with 10 million identical Variant Surface Glycoproteins (VSG) mold. Attached to the outer membrane via its A Glycosylphosphatidyl inositol (GPI) anchor. There, he has a variety of thousands of different VSG genes, which can be alternately expressed, he is always able to answer evasive. The presence of VSG on the trypanosome surface has also also more other. During infection an endogenous phospholipase C (PLC) enzyme namely the GPI anchor, causing VSG to be released in the circulation of the host. This liberated VSG is involved in the induction of Tumor Necrosis Factor (TNF), an inflammatory cytokine produced by the immune system of the host. The production of TNF contributes to a large extent in the development of the syndrome of trypanosomiasis (1). The research unit Cellular and Molecular Immunology (CMIM, VUB) specializes itself in the research of trypanosome-host interactions. Here, Trypanosoma brucei model, where unique attention to the role of TNF in both of the diagnosis control, also by the development of the disease or trypanosomiasis (1,2). A crucial aspect of the Infection where CMIM's recent has focused on is the fact that the infection-associated TNF induction is at the root of the anemia dying occurs during T. brucei infections. The cause for this is currently being investigated at the level of the effect of TNF on (i) erythrophagocytosis, (ii) the modulation of fatty acid metabolism and (iii) the modulation of the red blood cell (RBC) membrane. New results from my thesis show that TNF also affects erythropoiesis and that at trypanosome infections this process is suppressed at the level of the bone marrow stem cell (3). Coupled with the TNF study, CMIM recently paid attention to the role of this cytokine in B-cell mediated control of trypanosomiasis. It has recently been discovered that with the VRS of RBCs, B cells also occur during infection (4.5). From the initial results or my doctoral research that I, as a BAEF, initiated a bursal at the University of Massachusetts (UMASSAmherst, USA), it appears that this defect can also be largely attributed to a blockade of bone marrow stem cell differentiation of B-cell lymphopoiesis. The host should no longer be able to become new B cells during infection. This hypothesis forms the starting point of the eating process. 2. Problem and conclusion: B cells are crucial for Trypanosoma brucei parasite control, but this protective arm of the immune system is very efficient. What happens to CMIM? Is the research we have here on an analysis of modulations of pre-B cells. The aim is to block the mechanism of T. brucei parasites to suppress the process of hematopoises and to prevent the production of new B cells. The project Will investigate: (i) of Infection virulence, induction of inflammation and inhibition of B-cell lymphopoiesis linked Are, (ii) Which intracellular B-cell signal transduction kaskades are involved, (iii) of New intervention Strategies can be worked out Are dying the infection-associated inhibition of B-cell lymphopoiesis can counteract. This would make it possible to (i) Reduce the clinical picture of trypanosomiasis, and (ii) Would this allow the host to use his adaptive (B-cell) immune system more efficiently in the fight against the trypanosome.

Trefwoorden:Applied Biology

Disciplines:Biologische wetenschappen