Participação de eosinófilos na evolução da infecção experimental por Schistosoma mansoni em camundongos

Abstract

The severity of chronic schistosomiasis has been associated with the intensity and type of the granulomatous inflammation, a cellular response induced by secreted antigens from parasite eggs retained in the liver and intestine of the host. During acute schistosomiasis, about 50% of the cells that constitute the granuloma are eosinophils, however, the role of this cell in schistosomiasis pathology is not yet fully established. To investigate the role of eosinophils in the parasitic burden control, granuloma formation and evolution of morbidity induced by experimental infection of mice with S. mansoni, BALB/c genetically deficient in the differentiation of eosinophils (dblGATA) and BALB/c not deficient (WT) were infected subcutaneously with 25 cercariae of the LE S. mansoni lineage and followed for 12 weeks. During the entire period the mortality induced by the infection was monitored. After 8 (acute phase) and 12 (chronic phase) weeks of infection, animals from each experimental group were euthanized to estimate the parasitic load through the counts of worms recovered from the circulation and eggs retained in the liver and intestine and eliminated in the feces of each animal. In the same period, immunological and pathological evaluations were performed by the assessment of cellular infiltration, cytokine production, collagen deposition and granuloma measurement in the liver of experimental animals. During experimental schistosomiasis, the absence of eosinophils in dblGATA mice was confirmed by reduced EPO tissue activity and absence of cells with the typical eosinophils morphology on the histopathological evaluation. The absence of eosinophils was accompanied by lower MPO activity, but not in NAG activity, suggesting a selective reduction in the recruitment of granulocytes. In acute and chronic phase of schistosomiasis the number of worms recovered from circulation and the eggs retained in the liver or eliminated in the feces were similar in WT and dblGATA mice, however with greater retention of eggs in the intestinal tissue in animals deficient. dblGATA infected mice showed significant decrease in liver concentration of Th2 cytokines (IL-33, IL-13 and IL-5), IL-17 and regulatory cytokines (IL-10 and TGF-), and increase in Th1 cytokines (IFN- e TNF-), as compared to BALB/c WT animals, but there was no difference in IL-4 levels between the infected mice. The alterations of immune response of infected dblGATA was accompanied by higher infiltration of mononuclear cells and significant increase in the granuloma volume, but lower collagen deposition in liver of chronically infected deficient mice. Moreover, dblGATA mice showed a significant increase in serum transaminase levels (AST ALT), indicating greater liver damage. The current data indicate that eosinophils support the polarization of Th2 response and its modulation, affecting the control of tissue damage and progression of fibrosis during Schistosoma mansoni infection.