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Page 6 of 20 Varikuti et al. Vessel Plus 2020;4:28 I http://dx.doi.org/10.20517/2574-1209.2020.27

Table 1. Roles and mechanisms of vascular endothelium in malaria, leishmaniasis, toxoplasmosis, Chagas disease, and HAT
Parasite name Disease Role of VE Ref.
Plasmodium spp. Malaria Expresses receptors for Plasmodium antigens [72,73]
Reservoir for epoxide contains lipid signaling molecules and helps in [74]
multiplication of parasites
Produces low molecular weight growth factors, which enhance the parasite [75]
proliferation
Leishmania spp. Leishmaniasis Reservoirs for intra- and extracellular parasites [76]
Releases nitric oxide (NO) and limits the spread of the disease [77]
Expresses ICAM-1 in skin lesions in cutaneous disease, which helps lymphocyte [78]
migration s to sites of inflammation
Increases expression of VCAM-1, VEGF-A and VEGF-R in the skin lesions in [79-81]
cutaneous disease
Splenic endothelial cells express Ntrk2, helps in the pathological remodeling of [82]
the spleen in visceral disease
Toxoplasma. Toxoplasmosis Serves as replicative niche and provides the entrance to CNS [83]
T. gondii infection leads to activation of cerebral endothelial cells, facilitating the [84]
spreading of the disease
Trypanosoma spp. Chagas disease Key role in the dissemination of parasites to the other organs [85,86]
Produces various inflammatory molecules leading to trans-endothelial migration [85,87,88]
Releases vasoactive molecules such as endothelin-1 and pro-inflammatory [89-92]
cytokines IL-1β, iL-6, TNF-a, and thromboxane A2 leading to the production of
iNOS
Produces endothelin-1 and IL-1β, activated ERK1/2 and NF-kB, resulting in the [93-95]
induction of Cyclin-D1 in uninfected cells
Trypanosoma spp. Human African Serves as replicative niche [96,97]
trypanosomiasis Produces inflammatory cytokines such as TNF-a, IL-6, and IL-8 [98,99]
Induces the production of ICAM-1, E-selectin, and VCAM-1 to facilitate parasite [96,98,100]
migration into the central nervous system (CNS)
Facilitates parasite transit across the endothelium of cerebral blood vessels by [97,101]
the production of laminin-8, calcium, and papain-like cysteine proteases
VE: vascular endothelium; HAT: Human African trypanosomiasis; ICAM-1: intercellular adhesion molecule-1; VCAM-1: vascular cell
adhesion molecule-1; VEGF-A: vascular endothelial growth factor-A; VEGF-R: vascular endothelial growth factor receptor; IL: interleukin

Table 2. Roles and mechanisms played by exosomes in malaria, leishmaniasis, toxoplasmosis, Chagas disease, and HAT
Disease Exosomal Factors Cell origin Mode of Action Ref.
Malaria Parasitic components Infected Induces antigen presentation and elicit a long-term [102,103]
(protein, lipid, RNA, DNA) reticulocytes antibody protective immune response, increase
memory CD4+ and CD8+ T cells
Pathogen genes Infected RBCs Facilitates cell-to-cell communication between [104]
parasites, promote differentiation to sexual forms
Leishmaniasis Virulence factors and Parasite Induces secretion of IL-8 over TNF-a in host [105]
effector proteins macrophages
Alters the cytokine response of monocytes through [106]
upregulating IL-10 and inhibiting TNF-a production
Inhibits IL-12p70, TNF-a, and IL-10 cytokine functions in [107]
monocyte-derived DCs and prevent DC-induced naïve
T cell differentiation into mature Th1 cells
GP63 Parasite Exacerbates lesions due to increased production of [108]
inflammatory cytokine IL-17a and over the induction of
IL-4 and IL-10
Infected Regulates PTPs and TFs in target macrophages [109]
macrophages
Antigenic proteins Infected DCs Cleaves Dicer1 in hepatocytes to block miRNA-122 [110]
production, causing a decreased serum cholesterol level
Toxoplasmosis Antigenic proteins Infected DCs Induces protective spleen-derived Th1 and humoral [111,112]
immune responses with high levels of IgA antibody
Exosome Parasite Modulates macrophage activation through increased [113]
production of IL-12, TNF-a, and IFN-g and a decrease in
IL-10
PAMPs Parasite Induces protective cellular and humoral immune [53]
responses