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Amelioration of murine cerebral malaria by dietary restriction
N H Hunt1, N Manduci, C M Thumwood
1Department of Pathology, University of Sydney, NSW, Australia.
Abstract:
CBA/T6 strain mice infected with Plasmodium berghei ANKA develop cerebral symptoms and die, with mononuclear cell attachment to the cerebral microvascular endothelium, petechial haemorrhages and breakdown of the blood-brain barrier, some 6-7 days post-inoculation. The effects of dietary restriction on this process were examined. Mice were fed ab libitum (Group 1) or their food was restricted to produce body weight loss of 1.0-2.0% (Group 2), 2.5-3.5% (Group 3), 4.0-6.5% (Group 4) or 7.0-9.5% (Group 5) relative to Group 1. Dietary restriction reduced deaths caused by cerebral malaria from 100% in Group 1 to 47% (Group 2), 43% (Group 3), 10% (Group 4) and 53% (Group 5). Restriction of food intake had no effect on (1) the progression of parasitaemia in infected mice (2) changes in haematocrit, spleen weight, total lymph node cell number or (3) peritoneal exudate cell number in either malaria-infected or uninfected mice. P. berghei ANKA infection did not significantly affect the proportion of lymph node leucocytes that were Thy-1+ T cells or CD8+ T cells, but did lead to significant increases in the CD4+ and B cell populations. Dietary restriction alone increased the lymph node CD4+ cell population but did not affect the increase in B cells in malaria-infected mice. P. berghei ANKA infection and dietary restriction together did not lead to increased CD4+ cell numbers in lymph node leucocytes. The in vitro proliferative response to isolated lymph node cells to concanavalin A or phorbol myristate acetate plus ionomycin was measured and found to be identical in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Dietary restriction significantly reduces deaths from cerebral malaria in mice infected with Plasmodium berghei ANKA. This intervention did not affect parasite levels or immune cell counts, highlighting its specific protective effect against severe malaria outcomes.
Area of Science:
- Immunology
- Parasitology
- Nutritional Science
Background:
- Cerebral malaria, caused by Plasmodium berghei ANKA infection in CBA/T6 mice, leads to severe symptoms and mortality.
- Pathological hallmarks include mononuclear cell adhesion, petechial hemorrhages, and blood-brain barrier disruption.
Purpose of the Study:
- To investigate the impact of dietary restriction on the development of cerebral malaria.
- To assess how varying levels of food intake affect mortality and immune responses during Plasmodium berghei ANKA infection.
Main Methods:
- Mice were subjected to different levels of dietary restriction, ranging from ad libitum feeding to significant body weight loss.
- Mortality rates, parasitemia progression, hematocrit, spleen weight, and immune cell populations (T cells, B cells) were monitored.
- In vitro lymphocyte proliferation assays were conducted.
Main Results:
- Dietary restriction markedly reduced mortality from cerebral malaria, with optimal protection observed at 4.0-6.5% body weight loss.
- No significant effects of dietary restriction were found on parasitemia, hematocrit, spleen weight, or peritoneal exudate cell counts.
- While infection increased CD4+ and B cells, dietary restriction alone increased CD4+ cells; combined effects did not further elevate CD4+ numbers.
- Lymphocyte proliferative responses remained consistent across all groups.
Conclusions:
- Dietary restriction offers significant protection against mortality in experimental cerebral malaria.
- The protective mechanism appears independent of effects on parasite load, hematological parameters, or general immune cell proliferation.