REGULATION OF TRYPANOSOMA-CRUZI INFECTION IN MICE BY GAMMA-INTERFERONAND INTERLEUKIN-10 - ROLE OF NK CELLS

Gamma interferon (IFN-gamma) plays an important role in experimental T rypanosoma cruzi infections, presumably by controlling the early repli cation of parasites in host macrophages, In this work we show that NK cells represent an important cell type responsible for the production of most of the IFN-gamma in the early stages of T. cruzi infection and that the in vivo treatment of mice with anti-NK1.1 monoclonal antibod y made resistant animals susceptible to the infection. Through in vitr o experiments, we demonstrate that normal splenocytes from euthymic or athymic nude mice cultivated for 48 h with live T. cruzi trypomastigo tes produced elevated levels of IFN-gamma. In addition, NK-depleted sp lenocytes show a drastic reduction of IFN-gamma production in response to live T. cruzi trypomastigotes. We also demonstrate that IFN-gamma production is dependent on a factor secreted by adherent cells, Supern atants of spleen cells from athymic nude mice are able to induce IFN-g amma production by normal splenocytes when cultured with trypomastigot es, The addition of anti-interleukin-10 to these cultures resulted in a marked increase in IFN-gamma production. On the other hand, the abse nce of NK cells led to an increased secretion of interleukin-10 upon i n vitro stimulation with T. cruzi. Taken together, these results sugge st that NK cells are the major source of IFN-gamma that could he invol ved in limiting the replication of T. cruzi in host macrophages during the early acute phase of the infection.