Characterization of macrophage dysfunction in rodent malaria.

Abstract

Immunosuppression in malaria has been attributed, in part, to alterations in macrophage function. The present study was undertaken in an attempt to characterize the dysfunction and to determine if it is regional or if it occurs in different populations of macrophages. The resting O2 consumption of either hepatic, splenic, or peritoneal macrophages or polymorphonuclear neutrophils (PMNs) was unaltered by the malaria infection. However, the respiratory burst was significantly enhanced in the three macrophage populations but not in the PMNs. A significant increase in their phagocytic capacity and microbicidal activity was noted for hepatic and peritoneal but not splenic macrophages or PMNs. The malaria-infected mice had a marked decrease in serum antibody and splenic plaque response to bovine serum albumin (BSA) but not to keyhole limpet hemocyanin (KLH). Following an in vitro incubation with BSA, splenic macrophages from infected mice were not able to induce an antibody response when injected into normal mice. However, following incubation with KLH splenic macrophages could induce an adequate response in normal mice. This ability of macrophages from malaria-infected mice to transfer (or induce) a response in normal mice appeared to correlate with the amount of antigen digested, or perhaps retained, by the cells, i.e., BSA digestion was significantly less than KLH. These results indicate that the macrophage dysfunction in malaria is distinct depending on the tissue population that the macrophage is obtained from and that the impaired antibody response may be restricted to antigens requiring macrophage processing.