Immunological responses and the pattern of disease in mice infected with transfected Leishmania major constitutively expressing active IL-1alpha.
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 proinflammatory 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-1alpha by Leishmania parasites and to determine its effect on the parasite development. Leishmania constitutively producing IL-1alpha was engineered, using the pX63Hyg-IL-1alpha vector. IL-1alpha 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-1alpha production and its accessibility to the immunological cells might be important in the outcome of leishmanial infection.
Bersudsky
Marina
M
Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Laban
Avraham
A
El-On
Joseph
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D053582:Interleukin-1alpha / Q000096:biosynthesis* / Q000235:genetics; D018320:Leishmania major / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008018:Life Cycle Stages; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D011897:Random Allocation; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000913:Antibodies, Protozoan; D053582:Interleukin-1alpha