Extracellular Vesicles from Trypanosoma brucei Mediate Virulence Factor Transfer and Cause Host Anemia

Abstract

Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling inducing anemia.

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

“…The gp63 proteases, which are expressed by trypomastigotes and amastigotes (63), as well as several integral membrane proteins with transporter activity (Table S2), were also detected, which is consistent with the hypothesis that T. cruzi vesicles in the TESA preparation are derived primarily from the trypomastigote or amastigote plasma membrane (33,37,64). In addition, TESA EVs also contained a variety of proteins known to localize to the glycosome, flagella, mitochondria, nuclei, or cytosol (Table 1; Table S2), many of which have been previously detected in purified EVs from Leishmania and Trypanosoma brucei (38,41,65). Of note was the absence of glycolytic enzymes, which were previously observed in T. cruzi metacyclic trypomastigotes and epimastigotes and Leishmania EVs (33,38,41,53).…”

KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of Flagellar Membrane Proteins and Cell Division in African Trypanosomes

“…Recent studies on African trypanosomes have uncovered novel unexpected functions for flagella in these parasites. Szempruch et al (36) have reported that BF trypanosomes generate extracellular vesicles that originate from the flagellar membrane, contain flagellar proteins and virulence determinants such as serum resistance-associated protein, and deliver these vesicles to host cells including erythrocytes. This observation further underscores the importance of flagellar membrane proteins in the biology and virulence of African trypanosomes.…”

Not all extracellular vesicles were created equal: clinical implications

“…Furthermore, release of extracellular vesicles from nonmammalian cells may be involved in the pathogenesis of infectious disease. Thus, extracellular vesicles from Trypanosoma brucei mediate virulence factor transfer and erythrocyte remodeling, causing anemia (14).…”