[Biology of macrophages-Leishmania interactions]

Leishmania are trypanosomatidae which under their amastigote form behave as obligate intracellular parasites. At this stage, they multiply in macrophages of infected mammals (including man), within parasitophorous vacuoles (PV). These organelles of macrophage origin are part of the endocytic pathway. Study of their contents and membrane composition shows that they finally resemble lysosomes/prelysosomes. PV maintain a very acidic pH (< or = 5), and contain numerous functional lysosomal enzymes. They are limited by a membrane characterized by the presence of intrinsic and peripheral proteins described as being mainly associated with prelysosomal and/or lysosomal compartments (lamp-1, lamp-2, macrosialin, rab7p). Leishmania amastigotes appear to be acidophilic micro-organisms resistant to the action of lysosomal hydrolases and as such are fully adapted to the conditions encountered within prelysosomes/lysosomes. After stimulation of infected macrophages with interferon-gamma, we also note the presence of major histocompatibility complex (MHC) class II molecules in PV membrane but not that of MHC class I molecules. It is not yet known whether the PV-associated class II molecules play a role in the presentation of parasite antigens to protective specific T lymphocytes or whether parasites have developed strategies to inhibit or divert to their own advantage the antigen presentation process potentially detrimental to their survival. In any case, Leishmania-infected macrophages exhibit a deficiency in their capacity to present exogenous antigens in the context of MHC class II molecules. We are currently investigating whether this deficiency also extends to the presentation of parasite antigens.(ABSTRACT TRUNCATED AT 250 WORDS)