Stable RNA interference of host thrombospondin‐1 blocks Trypanosoma cruzi infection

Abstract

Interactions between Trypanosoma cruzi and the extracellular matrix play an important role in cellular invasion. Here we show that T. cruzi increases the levels of thrombospondin-1 (TSP-1) expression in host cells during early infection. Stable RNA interference of host cell TSP-1 knocks down the levels of TSP-1 transcripts and protein expression in mammalian cells causing inhibition of T. cruzi infection. Addition of TSP-1 to these cells restores infection. Thus, host TSP-1, regulated by the parasite, plays a crucial role in early infection. This is the first report showing that a human parasite modulates TSP-1 expression to facilitate infection.

Molecular analysis of early host cell infection by Trypanosoma cruzi

“…RNAi was recently used to reduce the expression of host genes involved in early T. cruzi infection of human epithelial cells (52,114). RNAi of extracellular matrix genes, laminin gamma-1 and thrombospondin 1 blocks T. cruzi infection (52,114). These are the first reports showing that knocking down the expression of human genes by RNAi inhibits the infection of an intracellular parasite.…”

“…cruzi is also able to increase the levels of thrombospondin-1 (TSP-1) expression in host cells during early infection. Stable RNA interference of host cell TSP-1 knocks down the levels of TSP-1 transcripts and protein expression in mammalian cells causing inhibition of T. cruzi infection (114). Addition of TSP-1 to these cells restores infection.…”

“…RNAi is already being used in basic science as a method to study the function of genes and it may lead to novel therapies in the future. RNAi was recently used to reduce the expression of host genes involved in early T. cruzi infection of human epithelial cells (52,114). RNAi of extracellular matrix genes, laminin gamma-1 and thrombospondin 1 blocks T. cruzi infection (52,114).…”

RNA interference and HIV‐1 infection

“…RNAi strategies have also been used to target a plethora of different mRNAs involved in diseases of distinct etiologic mechanisms, including cancer, diabetes, infectious diseases, etc. [57][58][59][60].…”

Drug Discovery by Aptamers in Protozoan Infectious Diseases

“…Thereby the parasite needs to build up parasite-host cell adhesion for initiation of the invasion process (Alves and Colli, 2008). Macromolecules on host cell surfaces such as laminin, thrombospondin, heparan sulfate, and fibronectin are believed to be involved in parasite-host cell contact , Simmons et al, 2006. Approaches have been undertaken to selectively interfere with parasite host cell receptors in order to inhibit the cellular invasion process of T. cruzi.…”