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Together with HIV/AIDS and tuberculosis, malaria is a major infectious disease. Two thirds of the global population is at risk for malaria with sub-Saharan Africa accounting for about 90% of the deaths. Morbidity due to severe complications of this disease is extremely high among young children and pregnant women in this area. There is currently no vaccine available and drugs and insecticides are losing their effectiveness as the parasite and mosquito vectors, respectively, develop resistance to these tools of control. The major focus of the work in my laboratory is elucidation of the mechanisms of protective immunity against blood-stage malaria. One of our aims is to identify the cells and cytokines responsible for initiating innate immunity and inducing adaptive immunity to intraerythrocytic Plasmodium parasites, the causative agents of malaria. For our studies, we use a murine model of malaria in resistant and susceptible inbred mice infected with the rodent parasite, P. chabaudi AS. This rodent parasite is considered to have many similarities to the major human malaria parasite P. falciparum. We have identified that dendritic cells, NK cells, macrophages, and CD4+ T helper cells play important roles in the cell-mediated and antibody-dependent innate and adaptive immune responses required to control blood parasitemia and to clear and resolve the infection. We have also identified that a network of cytokines, involving IFN-gama, IL-12, TNF-alpha and GM-CSF, is critical for the development of protective immunity. Since anemia is a major cause of morbidity and mortality in children and pregnant women with severe malaria in sub-Saharan Africa, we are also examining cytokine regulation of erythropoiesis using in vivo and in vitro approaches. In collaboration with Dr. Philippe Gros, we are also identifying the major genes and their functions involved in susceptibility to malaria using the approaches of whole genome scanning, positional cloning and the candidate gene approach as well as transcriptional profiling of target tissues using cDNA microarrays and identification of important cell phenotypes by flow cytometry. Information obtained from our studies is important for the development of an efficacious vaccine strategy against blood-stage P. falciparum infection.