Cerebral malaria is regulated by host mediated changes inPlasmodiumgene expression

Abstract

AbstractCerebral Malaria (CM), the deadliest complication ofPlasmodiuminfection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between: ECM susceptible C57BL/6 mice infected with ECM-causingPlasmodiumANKA (PbANKA) parasites (ANKA(C57BL/6)); ECM resistant Balb/c mice infected withPbANKA (ANKA(Balb/c)); and C57BL/6 mice infected withPbNK65 that does not cause ECM (NK65(C57BL/6)). All ANKA(C57BL/6)mice developed CM. In contrast in ANKA(Balb/c)and NK65(C57BL/6)infections do not result in CM and proceed similarly in terms of parasite growth, disease course and host immune response.. However, parasite gene expression in (ANKA(C57BL/6)) was remarkably different than in ANKA(Balb/c)but similar to the gene expression in NK65(C57BL/6). Thus,PbANKA has a ECM-specific gene expression profile that is only activated in susceptible hosts providing evidence that the host has a critical influence on the outcome of infection.