Molecular mechanisms of host cell invasion by Trypanosoma cruzi

Abstract

The protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, is an obligate intracellular protozoan pathogen. Overlapping mechanisms ensure successful infection, yet the relationship between these cellular events and clinical disease remains obscure. This review explores the process of cell invasion from the perspective of cell surface interactions, intracellular signaling, modulation of the host cytoskeleton and endosomal compartment, and the intracellular innate immune response to infection.

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

“…The parasite-endothelial cell interactions are among the first to occur during acute T. cruzi infection and in recent years the nature of these interactions as well as their consequences have received increased interest. Some authors have proposed that endothelial cells and/or macrophages allow parasite entry into different organs (Epting et al, 2010).…”

Chagasic Cardiomyopathy

“…Transialidase, glycosylphosphatidylinositol (GPI) anchors surface-bound proteins are in charge of transferring sialic acid residues from the host cell to the parasite glycoproteins. This mechanism seems to be crucial in invasion given that trypomastigotes with no expression of trans-sialidases were poorly invasive to non-phagocytic cells (Epting et al, 2010). Also, infection by oral route involved other parasite glycoproteins such as mucin-like gp35/50 or gp82 on the surface of the trypomastigotes, resistant to protease digestion.…”

“…cruzi can reach the mammalian host cells via different mucosal tissues (i.e., conjunctiva, oral) or directly into blood (transfusion or congenital). The parasite in vivo can invade a vast range of cells such as monocyte/macrophages, dendritic cells, endothelial cells, fibroblasts, astrocytes, skeletal muscles, enteric nerves, and cardiomyocytes (Epting et al, 2010). Parasite invasion is a multistep process when several T. cruzi glycoproteins bind surface molecules on the host cells.…”

“…Before reaching the target tissues, T. cruzi must interact with the endothelial cells to actively penetrate or increase endothelium vasodilatation. Parasite protease can produce inflammations that increase vascular permeability (Epting et al, 2010). Several parasite proteases and glycoprotein expressed by trypomastigotes have been associated with invasion: gp60 (penetrin) gp63, gp35/50, gp82, gp90 a parasite glycosidase, mucins and transialidase such as gp85 or Tc85.…”

Análise proteômica de células não fagocíticas na fase inicial da infecção por trypanosoma cruzi

“…Esse processo gera uma reorganização do citoesqueleto da célula hospedeira, que resulta na formação do vacúolo ácido, denominado vacúolo parasitóforo, que envolve o parasito para internalização do mesmo (Epting, Coates, & Engman, 2010;Maeda, Cortez, & Yoshida, 2012;Tardieux, Nathanson, & Andrews, 1994a) .…”