A Toll/IL-1R/resistance domain-containing thioredoxin regulates phagocytosis in Entamoeba histolytica (56.23)

Abstract

Abstract Entamoeba histolytica is a parasite protozoan that infects humans and causes amebiasis in developing countries. Phagocytosis of epithelial cells, erythrocytes, leucocytes, and commensal microbiota bacteria is a major pathogenic mechanism used by this parasite. A Toll/IL-1R/Resistance (TIR) domain-containing protein is required for bacterial phagocytosis in the social ameba Dyctiostelium discoideum, both for nutrition and for protection against infection. In insects and vertebrates, TIR domain-containing proteins regulate phagocytic cell activation. Therefore, we investigated whether E. hystolytica expresses TIR domain-containing molecules that may be involved in the phagocytosis of erythrocytes and bacteria. Using Hidden Markov models (HMM), we identified an E. histolytica thioredoxin containing a TIR-like domain. The primary structure of this putative TIR domain exhibited low similitude with the TIR domain of human Toll-like Receptor (TLR)-2; however, the predicted tertiary structures of these two TIR domains were remarkably similar. Interestingly, the phagocytosis of erythrocytes and E. coli by E. histolytica trophozoites increased after the inhibition of the expression of thioredoxin using a specific siRNA. This suggests that TIR domain-containing thioredoxin is a negative regulator of phagocytosis in E. histolytica.