Extracellular Vesicles in Trypanosomatids: Host Cell Communication

Abstract

Trypanosoma cruzi, Trypanosoma brucei and Leishmania (Trypanosomatidae: Kinetoplastida) are parasitic protozoan causing Chagas disease, African Trypanosomiasis and Leishmaniases worldwide. They are vector borne diseases transmitted by triatomine bugs, Tsetse fly, and sand flies, respectively. Those diseases cause enormous economic losses and morbidity affecting not only rural and poverty areas but are also spreading to urban areas. During the parasite-host interaction, those organisms release extracellular vesicles (EVs) that are crucial for the immunomodulatory events triggered by the parasites. EVs are involved in cell-cell communication and can act as important pro-inflammatory mediators. Therefore, interface between EVs and host immune responses are crucial for the immunopathological events that those diseases exhibit. Additionally, EVs from these organisms have a role in the invertebrate hosts digestive tracts prior to parasite transmission. This review summarizes the available data on how EVs from those medically important trypanosomatids affect their interaction with vertebrate and invertebrate hosts.

Keywords: Leishmania; Trypanosoma brucei; Trypanosoma cruzi; extracellular vesicles; inflammation; innate immunity; insect vector; skin pathology.

Figure 1

Timeline of Trypanosoma cruzi EVs studies.

Figure 2

Mechanisms of EV involved in host-parasite interactions. The diagram represents the major contributions of EVs from T. cruzi, Leishmania sp. and host cells during the infection by these parasites. T. cruzi release heterogeneous populations of EVs containing surface mucin-like glycoproteins (tMuc and eMuc), GPI anchored proteins (GP63 protease, GP85, and TS superfamily members) and soluble proteins (cruzipain, Cz), which interact with macrophages through TLR2 receptors which activate MAP kinases and induce a pro-inflammatory response (TNF-α, IL-12, and IL-6). Macrophages also release EVs that might affect the host immune system. The TLR2—T. cruzi EVs interaction enhances further parasite invasion. In the insect vector, the parasite epimastigote EVs delays translocation of parasites through intestine. Leishmania metacyclics release EVs enriched with GP63 and LPG, that could interact with macrophages via TLRs and, depending on the species, to induce pro- and anti-inflammatory responses. GP63-enriched EVs were found to induce host protein tyrosine phosphatases concurring to alter macrophage signaling and microbicidal functions. However, receptors involved in EVs recognition concurring to augment infection of phagocytes is still not identify. Leishmania virus (LRV1) incorporate within Leishmania exosomes was found to induce myeloid cells (macrophage, neutrophil) inflammasome in a TLR-dependent fashion concurring to exacerbate skin pathology. Leishmania exosomes are released in the gut of the sand Fly vector and have been found to be co-inoculated with promastigotes during blood meal. Revealing that this co-inoculation can exacerbate myeloid cells infection and skin pathology development.