Aspectos da glicobiologia de Tripanosomatídeos: as vesículas extracelulares de Trypanosoma cruzi e o lipofosfoglicano (LPG) de Leishmania amazonensis na interação parasito-hospedeiro

Abstract

Tripanosomatid parasites are the causative agents of a wide spectrum of clinical manifestations. The parasites have an outstanding ability to avoid destruction in the hostile environments during their life cycles. Their main strategies include the expression of major glycoconjugates attached to the membrane by glycosylphosphatidylinositol (GPI) anchors. The GPI-mucins are important glycoconjugate of Trypanosoma cruzi. Those molecules play an important role on the protozoan infection and survival. Trypomastigote forms of T. cruzi shed extracellular vesicles (EVs) enriched with trans-sialidase (TS)/gp85 glycoproteins and other a-galactosyl (a-Gal)-containing glycoconjugates, like mucins. However, the role of EVs from different T. cruzi strains and some aspects of the immune system stimulation remain unknown. Here, vesicles from pathogenic (Colombiana (Tc I), YuYu (Tc I), Y (Tc II)) and non-pathogenic (CL-14 (Tc IV)) T. cruzi strains were purified and exhibited differences in their protein and a-galactosyl contents. Later, those polymorphisms wereevaluated in the modulation of immune responses (innate and in the chronic phase) in C57BL/6 mice. EVs from YuYu and CL-14 strains induced higher levels of proinflammatory cytokines (TNF-a and IL-6) and nitric oxide by macrophages via TLR2. In general, no differences were observed in MAPKs activation (p38, JNK and ERK 1/2) after EV stimulation. In splenic cells derived from chronically infected mice,a different modulation pattern was observed, where Colombiana and Y strain EVs were more pro-inflammatory. This modulation was independent of the strain used in the mice infection. To test the functional importance of this modulation, the expression of intracellular cytokines after in vitro exposure was evaluated using EVs from YuYu andColombiana strains. Both EVs induced cytokine production with the appearance of IL- 10 in the chronically infected mice. A high frequency of IL-10 in CD4+ and CD8+ T lymphocytes was observed. A mixed profile of cytokine induction was observed in B cells with the production of TNF-a and IL-10. Finally, dendritic cells produced TNF-a after stimulation with EVs. Intraspecific variation in T. cruzi EVs are very important to immune system activation and it is responsible to modulate the immunopatologycal events in acute and cronic Chagas disease.