THE FATE AND PERSISTENCE OF LEISHMANIA-MAJOR IN MICE OF DIFFERENT GENETIC BACKGROUNDS - AN EXAMPLE OF EXPLOITATION OF THE IMMUNE-SYSTEM BY INTRACELLULAR PARASITES

Leishmania spp. are intracellular protozoan parasites that are deliver ed within the dermis of their vertebrate hosts. Within this peripheral tissue and the draining lymph node, they find and/or rapidly create d ynamic microenvironments that determine their ultimate fate, namely th eir more or less successful expansion, and favour their transmission t o another vertebrate host though a blood-feeding vector. Depending on their genetic characteristics as well as the genetic make-up of their hosts, once within the dermis Leishmania spp. very rapidly drive and m aintain sustained T cell-dependent immune responses that arbitrate the ir ultimate fate within their hosts. The analysis of the parasitism ex erted by Leishmania major in mice of different genetic backgrounds has allowed us to recognize some of the early and late mechanisms driven by this parasite that lead to either uncontrolled or restricted parasi tism. Uncontrolled parasitism by Leishmania major characterizing mice from a few inbred strains (e.g. BALB/c) is associated with the expansi on of parasite reactive Th2 CD4 lymphocytes and results from their rap id and sustained activity. In contrast, restricted parasitism characte ristic of mice from the majority of inbred strains results from the de velopment of a polarized parasite-specific Th1 CD4 response. This muri ne model of infection has already been and will continue to be particu larly instrumental in dissecting the rules controlling the pathway of differentiation of T cells in vivo. In the long run, the understanding of these rules should contribute to the rational development of novel immunotherapeutic interventions against severe infectious diseases.