Benznidazole treatment during early indeterminate Chagas' disease shifted the cytokine expression by innate and adaptive immunity cells toward a type-1 modulated immune profile.

Trypanosoma cruzi-infected children was treated with benznidazole (Bz) duringthe early-indeterminate disease (E-IND) and the cytokine pattern of innate andadaptive immune compartments were evaluated prior to the treatment and1 year after it. At first, we observed that the ex vivo cytokine profile of circula-ting leukocytes from E-IND (n ? 6) resembled the one observed for healthyschoolchildren (n ? 7). Additionally, in vitro stimulation with T. cruzi anti-gens drove the E-IND cytokine pattern toward a mixed immune profile withhigher levels of IFN-c+, TNF-a+and IL-4+NK cells, increased numbers ofIFN-c+, TNF-a+and IL-10+CD4+T cells in addition to enhanced frequencyof TNF-a+/IL-4+CD19+lymphocytes. Interestingly, upon T. cruzi antigen invitro stimulation, E-IND CD8+lymphocytes displayed a selective enhancementof IFN-c expression, accounting for a global type 1-modulated cytokine micro-environment. A shift toward a type 1-modulated profile was also the hallmarkof Bz-treated children (E-INDT). In this context, despite the mixed overall exvivo cytokine profile observed for NK and CD8+T cells, incr eased ability ofthese leukocytes to produce IFN-c in respons e to T. cruzi antigens was repor-ted. Most noteworthy was the IL-10 production evidenced at T lymphocytes,mainly CD4+cells, as well as B lymphocytes, both ex vivo and upon antigenstimulation. Toget her, these findings gave evidence that NK cells and CD8+T lymphocytes are the major sources of IFN-c, a pivotal cytokine for successfultherapeutic response in human Chagas? disease. Moreover, our data have alsobrought additional information, pointing out IL-10 production by CD4+cellsand B lymphocytes, as the putative key element for parasite clearance in theabsence of deleterious tissue damage