Macrophage heterogeneity, antigen presentation, and membrane fluidity: Implications in visceral leishmaniasis

Morphological and functional heterogeneity of the splenic macrophage (M phi ) population was studied in Leishmania donovani (LD) infected BALB/c mice. On a discontinuous percoll gradient two distinct M phi populations were sep arated. They differed significantly in size as evident from Scanning Electr on Microscopy (SEM). Morphologically, the bigger M phi (LM) showed surface projections, whereas the smaller M phi (SM) was round. As regards the antig en-presenting abilities, the LM of infected animals showed defective antige n-presenting abilities at a later stage of the disease, i.e. 6 months post infection (I-6-LM) but not earlier, whereas the SM population remained func tionally intact throughout the course of the infection. Further, the I-6-LM showed a much enhanced A(d) status as compared to their controls. Interest ingly, both the I-6-LM and the control set showed a comparable level of bin ding of a known A(d) restricted peptide. Despite the presence of sufficient A(d) molecules and the ability to hind the appropriate peptide. I-6-LM wer e unable to stimulate peptide specific T-cell hybridoma. Further, the I-6-L M showed an increase in membrane fluidity and distorted morphology with mem brane fissure and blebs as evident from SEM. It is possible that an increas e in the membrane fluidity may lead to the defective antigen-presenting abi lity of I-6-LM. Thus, the LD infection functionally keep the I-6-LM out of antigen presentation and this may contribute to the defective cell mediated immune response in leishmaniasis.