Trypanosoma cruzitrans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling

Abstract

Patients infected with

Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation

“…These abundant parasite proteins have been implicated in mediating attachment of T. cruzi to mammalian cells (Magdesian et al, 2001;Ming et al, 1993;Pereira et al, 1996) and stimulation of PI 3-kinase/Akt-dependent pro-survival pathways in neuronal cells was shown to be mediated by transsialidase (Chuenkova et al, 2001;Chuenkova and Pereira, 2000). Although the complexities of the early interactions of T. cruzi trypomastigotes with mammalian host cell interactions are still emerging, the extent to which specific early signaling pathways are engaged by this parasite during the infective process are likely to have important downstream consequences with respect to regulation of host cell gene expression (Vaena de Avalos et al, 2002) and intracellular survival (Chuenkova et al, 2001).…”

“…This is an intriguing observation considering that PI 3-kinases direct a broad range of membrane trafficking events and may therefore participate in the regulation of the lysosome-mediated entry pathway. In addition, signaling events activated downstream of PI 3-kinase in response to live trypomastigotes or T. cruzi surface proteins of the trans-sialidase family (Schenkman et al, 1991) are capable of triggering anti-apoptotic cascades in host cells (Chuenkova et al, 2001;Chuenkova and Pereira, 2000). Thus, PI 3-kinase-dependent T. cruzi invasion, promoted through the engagement of one or more host cell surface receptors (Giordano et al, 1994;Magdesian et al, 2001) by heterogenous parasite surface proteins may have important implications for intracellular survival of this pathogen in the host (Chuenkova et al, 2001).…”

Implications of genetic variability of Trypanosoma cruzi for the pathogenesis of Chagas disease

“…A principal surface glycoconjugate from T. cruzi, GIPL, has been shown to induce macrophage apoptosis through its lipid ceramide domain 65 . Paradoxically, there is evidence that the parasites can inhibit host cell apoptosis, such that parasitederived molecules can interfere in cell growth.…”

“…Paradoxically, there is evidence that the parasites can inhibit host cell apoptosis, such that parasitederived molecules can interfere in cell growth. For example, T. cruzi trans-sialidase can impede nerve cell apoptosis, since it can activate expression of the bcl-2 gene, leading to the protection of rat pheochromocytoma PC12 cells (a lineage that displays various neuronal characteristics) against apoptosis induced by growth factor deprivation 65 . It is thus reasonable to suggest that among the molecules released by the parasite, those conferring a selective advantage to it represent potential targets for the development of treatment strategies to moderate the host immune system dysfunction 65 .…”

“…Throughout these nine decades, much has been discovered on the biological characteristics involving Chagas disease, such as: T. cruzi genetic diversity and the mechanisms of the parasite's entry into the host cell as regards the signaling pathways involving surface molecules on both the parasite and host cell, allowing the parasite to reach the cytoplasm and to replicate 3 ; factors released by the parasite that elicit different inflammatory responses, that may or may not lead to host cell apoptosis 64,65 ; mechanisms in the integration of T. cruzi kDNA fragments into the host cell genome, functioning as mutations that lead to changes in the host cell phenotype, evoking the immune system's rejection of cells containing the mixture of the expression of its proteins with those of the inserted kDNA 3 ; and evidence that different clones present differential tissue tropism, depending on the biological form of the parasite during infection 2 .…”