Abstract
BackgroundAn appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies.MethodsPeripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status.ResultsThe data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status.ConclusionsThe pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.
Highlights
An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology
Malaria status at inclusion was found to associate with age and iron deficiency anemia, but not with zinc or magnesium deficiency [16]
There was no evidence that inflammation was associated with zinc deficiency, magnesium deficiency or iron deficiency anaemia malaria and age seemed to be associated with inflammation (Table 1)
Summary
An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. The pattern of Th cell types, and the associated cytokine profile, probably depends on the type of antigen-presenting cells and their cytokine milieu, and on regulatory T-cells that suppress the proliferation and activity of B cells and Th cells by the production of IL-10 and transforming growth factor (TGF)-β. Imbalance in these responses can result in an inefficient adaptive immune response to clear infection, and may contribute to pathological consequences. Several reports [7,8,9,10,11,12,13,14,15] have indicated possible roles of micronutrients on immune responses but either they have focused on other infections than malaria, or their effects have been evaluated in individuals older than five years, the age with the highest vulnerability to malaria
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