Leishmania species: models of intracellular parasitism

Leishmania species are obligate intracellular parasites of cells of the mac rophage-dendritic cell lineage. Indeed, the ability to survive and multiply within macrophages is a feature of a surprising number of infectious agent s of major importance to public health, including Mycobacterium tuberculosi s, Mycobacterium leprae, Listeria monocytogenes, Salmonella typhimurium, To xoplasma gondii and Trypanosoma cruzi. The relationship between such organi sms and their host cells is particularly intriguing because, not only are m acrophages capable of potent microbicidal activity, but in their antigen-pr esenting capacity they can orchestrate the developing immune response. Thus , to initiate a successful infection parasites must gain entry into macroph ages, and also withstand or circumvent their killing and degradative functi ons. However, to sustain a chronic infection, parasites must also subvert m acrophage-accessory-cell activities and ablate the development of protectiv e immunity. The leishmanias produce a wide spectrum of disease in mice, and as such they have provided excellent models for studying problems associat ed with intracellular parasitism. In recent years, largely using these orga nisms, we have made enormous progress in elucidating the mechanisms by whic h successful intracellular infection occurs. Furthermore, characterization of immunological pathways that are responsible for resistance or susceptibi lity to Leishmania has given rise to the Th1/Th2 paradigm of cellular/humor al dominance of the immune response.