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Page 14 of 20 Varikuti et al. Vessel Plus 2020;4:28 I http://dx.doi.org/10.20517/2574-1209.2020.27

component on the host immune system in causing parasitic disease may help in the development of a novel
approach of diagnostic tools and treatment. Further research on exosomes is necessary to search for the
candidate vaccine and drug development.

The VE provides effective immunological homeostasis that controls the inflammatory response, mainly
through the production of cytokines. The VE is an important target of parasite invasion and the parasite
interaction on the VE is responsible for the development of clinical manifestations. The trans-endothelial
migration of parasites is the major key step in establishing infection. Thus, more experimental studies are
needed to provide insights on the interaction of blood parasites and VE, trans-endothelial migration, and
the role of endothelial cytokine mediators in parasite dissemination. A better understanding may reveal the
way to find more anti-parasitic regimens.

To summarize, both the VE and exosomes regulate the entry of parasites, their multiplication, signaling
between the parasite and host cells, and dissemination to the other organs of the hosts. In addition, the
VE and exosomes modulate both the innate and adaptive immune responses and maintain the integrity
of the inflammatory process (summarized in Figure 1 and Tables 1 and 2). However, further studies are
needed for a thorough understanding of the mechanisms and roles played by the VE and exosomes in
parasite survival and disease progression. The novel mechanisms regulated by the VE and exosomes can be
considered as potential therapeutic targets to treat and control these human protozoan diseases.

DECLARATIONS
Author’s contributions
Contributed to the review conception, design, and writing of the manuscript: Varikuti S, Jha BK, Holcomb
EA
Read and approved the final version of the manuscript: Varikuti S, Jha BK, Holcomb EA, McDaniel JC,
Karpurapu M, Srivastava N, McGwire BS, Satoskar AR, Parinandi NL
Extended expertise in exosome biology: McDaniel JC
Offered expertise in exosome biology and macrophage biology: Karpurapu M, Srivastava N
Contributed expertise in infectious diseases and edited the manuscript: McGwire BS
Offered expertise in the protozoan parasitic diseases and immunology: Satoskar AR
Contributed expertise in vascular endothelial biology, signaling, and structure and function of exosomes
and had the complete oversight of preparing this manuscript: Parinandi NL

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported partly by grants from National Institutes of Health (R01AG059981 and
5R21AI138555-02).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.