Search

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) develop neurological symptoms and die 6--7-day post-inoculation in the absence of high parasitemia. The effects of chronic intake of a high-fat diet on this process are largely unknown. In this study, we assessed the effect of a high-fat diet on the host-parasite response to malarial infection. Mice were fed ad libitum with either standard or a high-fat diet for 8 weeks and afterwards were infected with PbA. PbA-infected mice feeding a standard diet presented blood parasitemia, hepatic and cerebral histopathological alterations, and hepatic injury with increased hemozoin deposition in the liver. By contrast, these changes were not observed in the malaria high-fat diet group. In addition, mice fed a high-fat diet did not develop the expected neurological symptoms of cerebral malaria and were resistant to death. Taken together, our results indicate that chronic ingestion of high-fat diet prevents the development of experimental malaria induced by PbA injection, suggesting a relationship between a high-fat diet and malaria, which is an interesting subject for further study in humans.

Infection of mice with Plasmodium berghei NK65 represents a well-recognized malaria model in which infection is accompanied by an intense hepatic inflammatory response. Enzyme-inducible nitric oxide synthase is an important regulator of inflammation and leukocyte recruitment in microvessels, but these functions have yet to be evaluated in experimental malaria. In this study, we assessed the involvement of inducible nitric oxide synthase in inflammatory responses to murine experimental malaria induced by P. berghei NK65. We observed that wild type (WT) and nitric oxide synthase (iNOS)-deficient mice (iNOS(-/-)) mice showed similar levels of parasitemia following P. berghei NK65 infection, although infected iNOS(-/-) mice presented early mortality. Inducible nitric oxide synthase deficiency led to increased leukocyte rolling and adhesion to the liver in iNOS(-/-) mice relative to the WT animals, as observed via intravital microscopy. Infected iNOS(-/-) mice also exhibited increased hepatic leukocyte migration and subsequent liver damage, which was associated with high serum levels of the cytokines TNF-α, IL-6 and IL-10. Our data suggest potential role for the iNOS enzyme as a regulator of hepatic inflammatory response induced by P. berghei NK65-infection, and its absence leads to exacerbated inflammation and sequential associated-hepatic damage in the animals., (Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Malaria is second only to tuberculosis as the leading cause of morbidity and mortality as a consequence of a single infectious agent. Much of the pathology of malaria arises from the inappropriate or excessive immune response mounted by the host in an attempt to eliminate the parasite. We here report the inflammatory changes observed in the cerebral microvasculature of C57BL/6 and BALB/c mice that had been inoculated with Plasmodium berghei NK65, a lethal strain of rodent malaria. Although no neurological signs were observed in experimentally infected mice, inflammation of the cerebral microvasculature was clearly evident. Histopathological analysis demonstrated that alterations in cerebral tissue were more intense in infected C57Bl/6 mice than in infected BALB/c animals. Intravital microscopic examination of the cerebral microvasculature revealed increased leukocyte rolling and adhesion in pial venules of infected mice compared with non-infected animals. The extravasation of Evans blue dye into the cerebral parenchyma was also elevated in infected mice in comparison with their non-infected counterparts. Additionally, protein levels of TNF-α, MIG/CXCL9, MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5 were up-regulated in brain samples derived from infected C57Bl/6 mice. Taken together, the data reported here illustrate the complex strain-dependent relationships between leukocyte recruitment, blood brain barrier permeability and chemokine production., (Copyright © 2011 Elsevier B.V. All rights reserved.)