Avaliação comportamental da resposta inflamatória frente a diferentes inóculos de trypanosoma cruzi em camundongos geneticamente modificados

Abstract

Introduction: An important strategy for containing the spread of the parasite is macrophage activation, as well as the use of nitric oxide as a potent trypanocidal agent. Studies indicate a range of responses as well as changes in parasitic behavior affecting the organic functioning through the concentration of inoculum of T. cruzi. Objectives: In this way we evaluate the inflammatory parameters in genetically modified mice infected with different inoculum of T. cruzi. Methods: 80 mice divided into C57BL/6 wild were used and C57BL/6 – iNOS-/- 10 weeks of age conforming groups: Control and infected with 3x102, 3x103 and 3x104 trypomastigote bloodstream forms of T. cruzi for each strain inoculated subcutaneously. Quantification of parasites in the blood was measured daily. After 9 days of infection the animals were placed in individual metabolic cages to collect urine in 24 hours and 10 days after infection were euthanized and necropsy. We collected blood for biochemical, heart to quantify the number of cells, nests of T. cruzi by immunohistochemistry and cytokines in the homogenate of the organ. Results: Parasites were found on the 3rd day (high inoculum) in both strains. WT peaked on day 7 up, 9 days for the average and 10 day for low inoculum, since iNOS -/- in all groups on the 10th day after infection. In the evaluation of ions, metabolites and enzymes, we noted an increase of urea and Glomerular Filtration Rate in WT, with a decrease of Urea, Protein and potassium urinary, plasma alkaline phosphatase, and albumin, inoculum dependent (p <0.05). Already in iNOS-/- an increase of urea, potassium, SGOT, SGPT, alkaline phosphatase, CPK, total protein and serum globulin. The difference in the number of cells and nesting T. cruzi/cm2 cardiac tissue showed an increased inoculum dependent for both strains. The cytokines profile showed no significant differences for iNOS-/- while the WT strain had increased IFN- γ, IL-12, TNF-α, IL-10 and IL-17 dependent inoculum and IL-4 decreased. Conclusion: There are variations in the host-parasite relationship in biological experimental Chagas disease between Wild Type and knockout iNOS-/- dependent on the concentration of inoculum.