Zinc requirement for macrophage function: effect of zinc deficiency on uptake and killing of a protozoan parasite

Abstract

The effects of suboptimal levels of zinc, an essential trace element, on the ability of murine macrophages to associate with and destroy a pathogenic parasite, Trypanosoma cruzi, were evaluated. Young adult A/J mice were fed zinc-deficient, zinc-adequate or restricted amounts of a zinc-adequate diet for 28 days. On the basis of weight loss and parakeratosis, the zinc-deficient mice were further divided into moderately and severely zinc-deficient on Day 28. Both the percentage of mouse peritoneal macrophages (MPM) with associated parasites and the number of parasites per 100 macrophages were significantly lower for macrophages from moderately and severely deficient mice compared to MPM from mice fed restricted or zinc-adequate diet. Furthermore, MPM from both zinc-deficient groups of mice killed fewer internalized parasites than did MPM from restricted or zinc-adequate mice. Pretreatment of MPM from zinc-deficient mice with 5 micrograms zinc/ml for 30 min completely restored both their capacity to take up and kill the parasites. Other trace metals tested, including copper, manganese and nickel, failed to reverse the effects of zinc deficiency. These results point to an important role for zinc in the biochemical events associated with macrophage uptake and killing of the parasite.