IFN-gamma, IL-4, IL-10 and IL-12 gene expression in BCG-Leishmania vaccination of Trypanosoma cruzi-infected mice

We have previously shown that vaccination of BALB/c mice with a combination of BCG pills killed Leishmania promastigotes, applied by the i.p. route 10 and 3 days before Trypanosoma cruzi inoculation, prolonged their survival and decreased their parasitaemia. In the present study we show that the BCG -Leishmania vaccine induced higher levels of circulating IFN-gamma in acute and chronic infection of mice [on day 25 and 40 post-infection (p.i.) resp ectively], in comparison to unvaccinated animals (PBS-treated). Though the IFN-gamma mRNA content of spleen cells of vaccinated and infected mice (on day 25 p.i.) was similar to that of unvaccinated animals. the BCG-Leishmani a vaccine enhanced significantly the production of IFN-gamma by spleen cell s stimulated with T. cruzi antigens. This effect was observed to a lower ex tent in BCG- and Leishmania-treated mice. The BCG-Leishmania vaccine reduce d the expression of the IL-10 mRNA of splenocytes as soon as day 12 p.i., b efore the peak parasitaemia. Such this effect was not observed in BCG- or L eishmania-treated animals. On day 25 p.i.. the BCG plus Leishmania- or BCG- treatment of mice abolished the capacity of spleen cells to produce IL-10 i n response to T. cruzi antigens. The levels of mIL-4 RNA and protein produc tion were not modified in any group of mice. T. cruzi infection in BCG Leis hmania-vaccined mice stimulated an early and high production of IL-12 trans cripts in spleen cells during the acute phase of the infection, that was pr olonged during the chronic phase of infection. This effect was weaker or ab sent in BCG- and Leishmania-treated animals. respectively. These results in dicate that the BCG-Leishmania vaccine stimulates the production of IL-12 a nd IFN-gamma, but inhibits that of IL-10 and is without effect on IL-4 when mice are infected with T cruzi. This highlights the kev role of endogenous ly produced IFN-gamma, IL-10 and IL-12 in the control of T. cruzi acute and chronic infection in mice and the favorable modulation of their balance by a vaccination combining BCG and Leishmania. (C) 2000 published by Elsevier Science Ltd. All rights reserved.