Immunopathology of experimental cutaneous leishmaniasis

Relatively susceptible BALB/c and relatively resistant A/J mice were infected subcutaneously in the right hind footpad with promastigotes of Leishmania mexicana amazonensis. A large localized lesion developed within 2 months after infection in the BALB/c mice, while A/J mice exhibited a small discrete fibrotic nodule. Sequential immunologic and histologic examination demonstrated that BALB/c mice developed a nodular foam-cell type of lesion and progressive depression of a delayed-type hypersensitivity (DTH) response to leishmania antigen, while the A/J mice had a mixed cellular fibrosing and encapsulating reaction and developed and maintained positive DTH responses to leishmania antigen. Anti-leishmania antibody responses were positive at similar levels in both strains. The lesions in BALB/c mice were found in bone marrow, tendon, skin appendages, and regional lymph nodes, with a tendency toward cutaneous metastases. Lesions in A/J mice remained localized. Fibrosis, focal fibrinoid necrosis, and lymphocytic and macrophagic infiltration were the outstanding features. Light and transmission electron microscopic studies indicated that no outstanding destruction of leishmanias seemed to occur within macrophages of either mouse strain. In the more resistant A/J mice, however, parasitized macrophages were frequently necrotic, and degenerating leishmanias were often seen free in the interstitial tissue. These observations help the interpretation of the histologic features, as well as the pathogenesis, of cutaneous and mucocutaneous leishmaniasis in man.