fig1

Figure 1. Schematic representation of cellular and molecular mechanisms played by vascular endothelium (VE) and exosomes in Plasmodium, Leishmania, Toxoplasma, and Trypanosoma spp. Infection. A: P. falciparum protein PfPTP-2 released through the exosomes from infected red blood cells (RBCs) facilitates cell-to-cell communication and promotes the differentiation of sexual forms of the parasites. P. falciparum erythrocyte membrane protein-1 (PfEMP1) and intercellular adhesion molecule-1 (ICAM-1) mediate the adhesion of infected erythrocytes to the VE and placental syncytioblasts; B: Leishmania parasites transport glycoproteins such as GP63 into the host cells through exosomes and regulate the protein tyrosine phosphatases (PTPs) and transcription factors such as NF-κB in macrophages. The PTPs prevent macrophage activation by inhibiting the secretion of IFN-γ, IL-12, and nitric oxide (NO). Leishmania infection also increases the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) to initiate an inflammatory response after migrating the mononuclear cells and lymphocytes to the endothelial cells; C: T. gondii parasites release exosomes, which contain HSP70 and CD63, as well as the T. gondii surface marker P30. These exosomes induce the production of IL-12, TNF-α, and IFN-γ and modulate macrophage activation; D: T. brucei releases exosomes that are deposited and fused to RBCs. The virulence factors of exosomes result in RBC membrane alteration and anemia. In addition, T. brucei activates the vascular endothelial cells by producing TNF-α, IL-6, and IL-8. The exosomes of T. cruzi contain C3 convertase binding protein, which helps the parasites to escape the complement-mediated lysis. T. cruzi releases cruzipain and invades vascular endothelium through a Ca⁺⁺-dependent mechanism