Gastrointestinal Nematode Infection Exacerbates Malaria-Induced Liver Pathology

Abstract

Mixed parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or severity of clinical disease. We have used the nonlethal malaria infection model of Plasmodium chabaudi AS in combination with the gastrointestinal nematode Heligmosomoides bakeri polygyrus to investigate the impact of nematode infections on malarial morbidity and antimalarial immunity. The data demonstrate that wild-type C57BL/6 mice coinfected with both parasites simultaneously exhibit a striking increase in mortality, while mice deficient in IFN-gamma or IL-23 survive coinfection. The increase in mortality in wild-type mice was associated with severe liver pathology characterized by extensive coagulative necrosis and an increase in hepatic IFN-gamma, IL-17, and IL-22 mRNA expression. This is the first demonstration of increased malaria-associated pathology associated with a switch toward a proinflammatory environment, involving not only IFN-gamma but also the IL-17/IL-23 axis, as a result of coinfection with a gastrointestinal helminth.