EVIDENCE FOR DIRECT INTERACTION BETWEEN MAST-CELLS AND LEISHMANIA PARASITES

When stimulated through IgE-(or IgG-) immune complexes with parasite a ntigens, mast cells can release several cytokines, including IL-4, IL- 6, IL-10, IL-12, lnterferon-gamma (IFN-gamma) and tumour necrosis fact or-alpha (TNF-alpha) that may influence the host response to Leishmani a major in modulating lesion size and persistence during experimental infection in the mouse. Moreover, recent data demonstrated that mast c ells ai-e able to be antibody-independently activated by direct contac t with bacteria, making them important elements in innate immunity. Gi ven these data, we asked whether cell-parasite contact could directly induce mast cell mediator release and whether mast cells could be infe cted by L. major or L. infantum parasites. In this study, we showed th at a pure homogeneous population of mouse bone marrow derived mast cel ls (BMMC) in contact with living L. major or L. infantum promastigotes , brit not with attenuated parasites or soluble parasite antigens, rel eased preformed mediators such as beta-hexosaminidase and the preforme d pool of TNF-alpha within minutes. Furthermore, direct cell-parasite contact induced TNF-alpha synthesis by mast cells within hours. Moreov er, we demonstrated by in vitro co-culture experiments that metacyclic L. major or L. infantum promastigotes are directly infective for a si gnificant proportion of BMMC and are transformed into intracellular am astigotes. Taken together, these data suggest that mast cell can parti cipate in the first line of defence, i.e. innate immunity during local cutaneous infection with Leishmania parasites.