In this context, several studies have suggested that the TNF-α/TNFR-mediated pathway plays a critical role in the process of T. cruzi control in the acute stage and the development of CCM, being TNFR1 closely linked to CD8+ T cell dysregulation (Michailowsky et al., 2001; Tzelepis et al., 2007). This evidence concerns the gene TNF and cerebral cavernous malformation.