Hannah Akuffo Project
The research area of my group is directed at a closer understanding of parasites in influencing the human host immune response. Specifically we have studied the participation of Natural Killer (NK) cells in Leishmania infection, the pathogenesis of ulcer formation during cutaneous leishmaniasis (CL) and the contribution of helminth infection in immunity to tuberculosis.
In 2006 I was appointed Adjunct Professor at MTC. For 80% of my time, I am the Head of the Division for University Support and National Research Development (UNI), at the Department of Research (SAREC), of the Swedish International Development cooperation Agency, Sida. The division is responsible for research, research training and other research capacity strengthening support to currently 12 countries in Africa, Latin America and Asia, namely Burkina Faso, Ethiopia, Mozambique, Tanzania, Rwanda, Uganda, Bolivia, Honduras, Nicaragua, Laos, Sri Lanka and Vietnam. In addition I represent Sweden on two boards (EMVI, European Malaria Vaccine Initiative & EDCTP, European and Developing Countries Clinical Trials Partnership) that work for developing products and clinical testing of interventions against malaria, TB and HIV/AIDS. In my own right a member of the Scientific and Technical Advisory Committee of the Tropical Disease Research (TDR) program based within WHO in Geneva.
The interplay between innate immunity as exemplified by NK cells, and Leishmania:
Our group was one of the first to show the importance of NK cells in human leishmaniasis .We have in 2006 shown (Lieke, T et al, manuscript) that the induction of interferon gamma (IFN-g), by Leishmania stimulated human NK cells is through a contact dependent mechanism, that leads to induction of cytotoxicity of NK cells and results in direct killing and destruction of the parasites. NK cells also suffer from the interaction and undergo necrosis. In addition we recently identified a Leishmania derived protein which inhibits NK function. Early NK cell response, especially release of IFN-g, is known to be crucial to direct the immune response towards Th1. Thus, such suppression of NK cells might have serious consequences for induction of effective immune response.
Understanding correlates of immunity to Leishmania
Our study on 'Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited' (Nylen S, et al Vaccine. 2006) questions how effective it is to use IFN-g as a correlate of protective immunity and also questions the logic behind the choice of leishmaniasis vaccine study individuals in endemic countries
Immunopathogenesis in cutaneous leishmaniasis:- the role of Fas/FasLigand and TRAIL induced apoptosis
Mechanisms of ulcer formation in leishmaniasis remains a mystery. We are one of few groups trying to understand the pathogenesis of ulcer formation. We have previously shown that Fas/FasL pathway is dysregulated both in human visceral leishmaniasis (VL) and CL. We propose a possible mechanism of ulcer formation during CL as apoptotic death of keratinocytes through enhanced FasL and TRAIL signaling (Eidsmo L et al. Am J Pathol. 2005 and in press). These data were further strengthened in a murine model of CL, where blocking the Fas/FasL system reduced ulcer formation during L. major infection. One student Liv Eidsmo defended her thesis entitled 'Dysregulation of Receptor Induced Apoptosis during Human Leishmaniasis: A Possible Mechanism of Skin Ulceration' in February 2006. Similar studies are ongoing to try to understand the mechanisms behind ulcer versus no-ulcer in Local CL (LCL) and Diffuse CL (DCL) following Leishmania aethiopica infection.
We have set up a mouse model of CL at MTC and will use it to further dissect the mechanisms involved during therapeutic interventions as well as to analyse NK cell interactions.
Deworming may improve BCG efficacy against tuberculosis:
BCG remains the gold standard as a vaccine against tuberculosis despite the differential efficacy in different parts of the world. We have shown that the presence of worms results in diminished BCG efficacy and propose that de-worming of individuals prior to vaccination may improve BCG efficacy in low income countries. Increased production of the downregulatory cytokine TGF-b but not enhanced Th2 cytokines is behind the helminth induced immunomodulation (Elias, D et al manuscript). Using a case-control study design we have shown that worm infections common in areas hyper-endemic for TB is a risk factor for active TB (Elias et al Trop Med Int Health, 2006).
Full Publication List 2000-2010