THE ROLE OF INTERFERON REGULATORY FACTORS IN THE PATHOGENESIS OF EXPERIMENTAL CEREBRAL MALARIA

Abstract

Human cerebral malaria is the most severe complications of P.falciparum infection. However, due to ethnical reasons, limited knowledge was obtained from human studies. As such, a mouse model, termed experimental cerebral malaria (ECM), is heavily relied on to study this pathology. In this model, an overwhelming host immune response characterized by a proinflammatory profile occurs. This dysregulated response is tightly controlled by transcription factors such as interferon regulatory factors (IRFs). Expression of IRF family is upregulated during PbA infection. In this project, we examined the role of three different transcription factors, IRF1, IRF3 and IRF7, in ECM development. IRF3 and IRF7, and to a lesser extent IRF1, are regulators of IFN-I and defect in IFN-I signalling protects mice from ECM death. Therefore, using mice deficient of each IRF, we investigate how each IRF controls the immune response during infection.