Immunological factors governing resistance and susceptibility of mice to Leishmania major infection.

Infection with Leishmania sp. is particularly suitable for the study of immunoregulatory mechanisms associated with host susceptibility or resistance. The clinical spectrum of this infection results from parasite virulence factors and host immune responses, some of which acting in a host protective manner while others exacerbate the disease. In the mouse model, factors governing resistance to Leishmania major infection mainly depends on the IFN-gamma activation of the leishmanicidal function of macrophages, and the Fas/ FasL-dependent T-cell cytotoxicity against infected macrophages. On the other hand, the immunological factors of susceptibility involve: I) the early upregulation of IL-4 production induced by the LACK antigen, II) the upregulation of IL-2 production, III) the high production of TGF-beta as macrophage deactivating factor, and IV) the production of IL-10 by the L. major infected macrophages, inhibited their microbicidal activity.