Host and parasite factors influencing the expression of cutaneous leishmaniasis

Host and parasite factors influencing the expression of cutaneous leishmaniasis were investigated in two murine models of different leishmanial diseases. The role of B lymphocytes in the uncontrolled disease manifested by BALB/c mice infected with cutaneous leishmaniasis was investigated in animals of this inbred strain depleted of B cells by neonatal administration of anti-mouse mu-chain antisera. Whereas non-depleted control mice developed chronic metastatic infections with both Leishmania tropica and Leishmania mexicana and showed depressed delayed-type hypersensitivity when skin-tested with leishmanial antigens, the mu-suppressed mice controlled their initial lesions while displaying strong antigen-specific delayed-type hypersensitivity. These findings reveal an inverse relationship between humoral and cell-mediated immunity in the expression of chronic leishmaniasis and suggest that B lymphocytes or their products regulate the delayed-type hypersensitivity response to leishmanial infection. In a separate study, healing and chronic strains of Leishmania were compared for their susceptibility to killing by lymphokine-activated mouse peritoneal macrophages. Whereas amastigotes of the healing strains were readily destroyed by these macrophages, amastigotes of two Leishmania strains, previously shown to produce chronic infections in mice, were resistant to killing by the same cells. These findings suggest that the ability of certain leishmanial strains to induce chronic disease may result from their capacity to evade intracellular destruction by activated macrophages.