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Statement of Research Interests

During my PhD thesis I was devoted to work on malaria, especially to study immune response against malaria antigens and to investigate some mechanisms occurring during the disease.
Immunity to clinical malaria is acquired after repeated infective mosquito bites. Transfer of gamma globulin from immune adults to malaria patients correlated with the control of parasitemia and febrile temperature (Cohen et al. 1961[1]). Furthermore, the IgG subclasses, particularly the cytophilic ones (IgG1 and IgG3), have been shown of particular importance since they have been repeatedly associated with protection against clinical falciparum malaria. Antibody class-switch, from IgM-IgD to IgG1-4, IgA1-2 or IgE is a highly regulated process under the control of cytokines and cellular interactions, involving B cells-produced CD40 and its ligand, CD154 (Good et al. 2006)[2]. However, in the field of malaria, factors responsible of the switching towards these two IgG subclasses are still unknown. Understanding the requirements for induction of cytophilic antibodies class switching in human B cells will improve anti-malarial vaccine development.
To address this question, we performed a study to elucidate the role of IL-21 cytokine, a γ-common chain cytokine produced by activated T helper lymphocytes, during a falciparum malaria infection. IL-21 regulates the functions of T cells, NK cell and myeloid cells; and also plays and important role on the development of B cells. Indeed, its role in atopic and tumor diseases has been well studied, few are known on its role on infectious diseases, including malaria. Previous studies have shown that IL-21 directs the antibody class switching toward IgG1 and IgG3 (Pene et al. 2004)[3]. Recently, we have shown that IL-21 levels were associated with both IgG1 and Ig3 antibody levels, in falciparum malaria patients in Gabon (Mewono et al. 2008)[4]. Indeed we did not exclude the involvement of other factors; the next step will be the characterization of those other factors. Indeed it is known that a combination of certain cytokines and B-cells activators have been shown to induce class switching to certain isotypes or subclasses in model systems. In the first step the focus is the characterization of other cytokines which, together with IL-21, might induce a switching towards IgG1 and/or IgG3. In the same way the assessment of the association of IL-21 and antibody levels directed against several malaria antigens will be done.
About the mechanisms, in malaria, the mechanism leading to severe malaria (severe anemia and cerebral malaria) is steel a matter of debate. However, it is now clear that it is the immune’s unbridled response against the parasite that causes the severity of the disease. In this line, we investigated the association between pro-inflammatory cytokines and levels of markers of endothelium damages. We found a positive association between levels of both sE-selectin and Thrombomodulin, with either TNF-α and INF-γ (Matondo Maya et al 2008)[5]. These associations brought us to suggest that E-selectin is connected with anemia and Thrombomodulin is implicated in the thrombosis. Blocking these two markers might protect against severe malaria.

List of cited references
1- Cohen, S., Mc, G. I., and Carrington, S. (1961) Gamma-globulin and acquired immunity to human malaria, Nature 192, 733-737. 2- Good, K. L., Bryant, V. L., and Tangye, S. G. (2006) Kinetics of human B cell behavior and amplification of proliferative responses following stimulation with IL-21, J Immunol 177, 5236-5247. 3- Pene, J., Gauchat, J. F., Lecart, S., Drouet, E., Guglielmi, P., Boulay, V., Delwail, A., Foster, D., Lecron, J. C., and Yssel, H. (2004) Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells, J Immunol 172, 5154-5157. 4- Mewono, L., Matondo Maya, D. W., Matsiegui, P-B., Agnandji, S. T., Kendjo, E., Barondi, F., Issifou, S., Kremsner, P. G., Mavoungou, E. (2008) Interleukin-21 is associated with IgG1 and IgG3 antibodies to erythrocyte-binding antigen-175 peptide 4 of Plasmodium falciparum in Gabonese children with acute falciparum malaria, European Cytokine Network 19, 1-7. 5- Davy W. Matondo Maya, Ludovic Mewono, Anne-Marie Nkoma, Saadou Issifou, Elie Mavoungou. Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation