Extracellular Vesicles in Chagas Disease: A New Passenger for an Old Disease

Abstract

Extracellular vesicles (EVs) are small lipid vesicles released by prokaryotic and eukaryotic cells containing nucleic acids, proteins, and small metabolites essential for cellular communication. Depending on the targeted cell, EVs can act either locally or in distant tissues in a paracrine or endocrine cell signaling manner. Released EVs from virus-infected cells, bacteria, fungi, or parasites have been demonstrated to perform a pivotal role in a myriad of biochemical changes occurring in the host and pathogen, including the modulation the immune system. In the past few years, the biology of Trypanosoma cruzi EVs, as well as their role in innate immunity evasion, has been started to be unveiled. This review article will present findings on and provide a coherent understanding of the currently known mechanisms of action of T. cruzi-EVs and hypothesize the implication of these parasite components during the acute and chronic phases of Chagas disease.

PARP1-cGAS-NF-κB pathway of proinflammatory macrophage activation by extracellular vesicles released during Trypanosoma cruzi infection and Chagas disease

“…It was shown that T. cruzi sheds compositionally different Ev depending on the developmental stage and virulence of the parasite strain [18,19], Ev shed by infective trypomastigote form of the parasite have high fusogenic potential with the host cell membranes [20], and contact with infective forms of the parasite also stimulated Ca 2+ -dependent shedding of membrane vesicles from THP-1 Mφ [21]. These and other studies did not explore the signaling cascades by which T. cruzi stimulates formation of membrane vesicles within itself or on the host cell membranes, though it was proposed that the host and parasite Ev may maintain cellular activation in CD [7]. Indeed, we recently showed that Ev released by human PBMCs exposed to T. cruzi infection activated a proinflammatory gene expression profile in THP-1 Mφ [3], a finding that strongly suggested that T. cruzi influences the host cell juxtacrine/paracrine Ev release and impacts the surrounding infected/non-infected cells and tissues.…”

“…Extracellular vesicles (Ev) are small vesicles harboring ligands, receptors, active lipids or RNA/DNA from the cell of their origin [7]. In pathological conditions, a stimulus that triggers Ev formation regulates the selective sorting of constituents and composition of Ev, and consequently, the biological information that they transfer.…”

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

“…Trypanosoma cruzi, the etiological agent of Chagas disease, infects macrophages during its trypomastigote stage and can generate both exosomes and ectosomes during infection (de Pablos Torro et al, 2018). The parasite then invades new cells and tissues after cellular differentiation and replication.…”

“…Interestingly, T. cruzi proteins are found inside host cells after their incorporation of T. cruzi EVs, and this insertion appears to be targeted at specific cells types such as fibroblasts, muscle and neuronal cells. In fact, parasite proteins have not been detected in other types of cells such as lymphocytes or erythrocytes (de Pablos Torro et al, 2018). EVs fusion with THP1 cells produce a higher expression of the genes IKBKB, NR3C1, and TIRAP, which have been associated with an increased generation of reactive oxygen species (ROS) and nitric oxide (NO) (Chowdhury et al, 2017).…”

Parasite, Compartments, and Molecules: Trick versus Treatment on Chagas Disease

“…Such glycoprotein diversity confers adaptation of the parasite to distinct environmental conditions. Morever, secretome of metacyclic trypomastigotes also demonstrated trans-sialidases and other surface molecules, playing a role in parasite invasion during acute and chronic infections [161,162]. The blockage of this process could be an interesting strategy in novel drug development.…”