Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPMOSIG, J. AlvarezBOMBEIRO, A. L.GONCALVES, L. A.MARINHO, C. R. F.PENHA-GONCALVES, C.LIMA, M. R. D'ImperioCHADI, G.2013-10-112013-10-112012IMMUNOLOGY, v.137, suppl.1, Special Issue, p.560-560, 20120019-2805https://observatorio.fm.usp.br/handle/OPI/2911Purpose/Objective: Neurological disorders have been described in children and in immunosuppressed hosts with Chagas’ disease, a Latin America protozoosis caused by Trypanosoma cruzi. Recently we showed that IL-12p40KO mice that were infected by T. cruzi, but not infected wild-type (WT) mice, develop a progressive paralysis that culminates in death. Objective: To analyze the elements involved in the neurodegenerative process presented by T. cruzi-infected IL-12p40KO (KO) mice. Materials and methods: KO and WT mice were infected by T. cruzi Sylvio X10/4 and submitted to behavioral analyses. Spinal cords (SCs) of both groups were analyzed every week by RT-PCR to estimate the kinetics of parasitism and immune transcripts, or analyzed by immunohistochemistry when KO mice presented complete paralysis to quantify neurons, astrocytes, macrophages/microglias, T. cruzi and other parameters. Results: Eye-seen and computerized behavior evaluation revealed that KO mice developed a progressive paralysis, from the tail to the forelimbs (p T. cruzi amastigotes, most of them inside macrophages/microglias. No lesions were observed in WT SCs. Compared to WT, KO SCs showed increased immunoreactive area for nitrotyrosine (239%, p T. cruzi 18S rRNA transcripts revealed the parasite was controlled in WT SC but kept increasing in KO SC (p T. cruzi transcripts were significantly lower in WT SCs. Conclusions: IL-12 and IL-23 efficiently act constraining T. cruzi parasitism in the CNS, occurring exacerbated inflammation and neurodegeneration in their absence.engrestrictedAccessMotor behavior dysfunction, neuronal death and glial activation in IL-12p40KO mice that were infected with Trypanosoma cruziconferenceObjectCopyright WILEY-BLACKWELLImmunology