Modulation of macrophage mannose receptor affects the uptake of virulent and avirulent Leishmania donovani promastigotes

The effect of oxidants and the anti-inflammatory steroid dexamethasone on t he attachment and internalization of virulent and avirulent Leishmania dono vani promastigotes by the macrophage mannosyl fucosyl receptor was examined . Oxidants and dexamethasone are known to down- and upregulate the expressi on of the mannose receptor. Macrophages, when treated with 500 muM H2O2 at 37 C for 30 min, stimulate about 45% inhibition in uptake of an avirulent s train (UR6), and 30 and 25% inhibition for virulent strains AG-83 and GE-I, respectively. Treatment of macrophages with dexamethasone for 20 hr result ed in a stimulation in uptake of the parasite. When UR6 was used, a 3-fold increase in uptake was observed compared with the controls. Parasite uptake was also inhibited by the H2O2-generating system, glucose/glucose oxidase; inhibition was blocked by catalase. Treatment of macrophages either with H 2O2 or dexamethasone did not affect the binding of the advanced glycosylati on end product-bovine serum albumin (AGE-BSA), the ligand for AGE receptor of macrophages. Similarly, indirect evidence also shows that both types I a nd 3 complement receptors (CR1, CR3) are not affected by these treatments, indicating that, besides the mannosyl fucosyl receptor, other receptors are minimally altered in the identified condition. These results suggest that the up- and downregulation of the mannose receptor of macrophages may play a role in affecting L. donovani infection.