Immunological responses and the pattern of disease in mice infected with transfected Leishmania major constitutively expressing active IL-1α

Immunity against leishmaniasis is mediated mainly by CD4⁺ T lymphocytes, which function by secreting cytokines, which in turn activate various effector mechanisms. Interleukin 1 (IL-1) represents one of the most pleiotropic pro-inflammatory cytokines and is required for normal regulation of Th1/Th2 responses. The aim of this study was to induce the expression of the inflammatory cytokine IL-1α by Leishmania parasites and to determine its effect on the parasite development. Leishmania constitutively producing IL-1α was engineered, using the pX63Hyg-IL-1α vector. IL-1α was produced by both promastigotes and amastigotes, and remained unchanged after transformation and development in mice. The protection against the disease achieved in BALB/c mice by the transfected parasites was superior to that obtained with the wild type. One month after infection a nodule was demonstrated in 22% and 60% of the mice inoculated with transfected parasites and the wild type, respectively. This tendency continued for an additional 2.5 months, after which the rate of infection increased to 90% and 100% in these two groups, respectively. The present study suggests that, during initial infection, the pathway of IL-1α production and its accessibility to the immunological cells might be important in the outcome of leishmanial infection.