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

Abstract

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