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

Vector Borne Zoonotic Dis. 2005 Winter;5(4):324-9. doi: 10.1089/vbz.2005.5.324.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Antibodies, Protozoan / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression
  • Interleukin-1alpha / biosynthesis*
  • Interleukin-1alpha / genetics
  • Leishmania major / genetics
  • Leishmania major / growth & development
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Life Cycle Stages
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plasmids / genetics
  • Random Allocation
  • Time Factors
  • Transfection / methods

Substances

  • Antibodies, Protozoan
  • Interleukin-1alpha