Motor behavior dysfunction, neuronal death and glial activation in IL-12p40KO mice that were infected with Trypanosoma cruzi
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Tipo de produção
conferenceObject
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
MOSIG, J. Alvarez
BOMBEIRO, A. L.
GONCALVES, L. A.
MARINHO, C. R. F.
PENHA-GONCALVES, C.
LIMA, M. R. D'Imperio
Citação
IMMUNOLOGY, v.137, suppl.1, Special Issue, p.560-560, 2012
Resumo
Purpose/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.