**5. Conclusion**

With the expansion of knowledge in parasitic diseases, the critical function of EVs became more evident in the development of the diseases. EVs applies many strategies not only to provide the survival and reproduction of *Leishmania* parasites inside the host, but also to enable the invasion by means of immune strategies including change in host antigens, development of self-tolerance, immune inactivation, immunosuppression and intervention of molecule-mimetic mechanisms between parasites and host antigens [16, 24, 25]. Recent studies propose that the parasites actually utilize the EVs as one infection strategy [18, 20, 21, 26–31], where the questions are arisen on how EVs modulate the host immune system and ultimately cause the infection. Based on the cell of origin, the release mechanisms of EVs from different protozoan parasites, including Apicomplexa and Kinetoplastids such as *Leishmania* species (spp.) [22, 23, 26, 32–35], *Plasmodium spp.* [31, 36–41], *Toxoplasma spp.* [36, 42, 43] and *Trypanosoma spp.* [44–49] were described, where the parasitic infections were studied in detail for leishmaniasis, malaria, toxoplasmosis and Chagas disease independently.

Several studies indicated that *Leishmania* exosomes can modulate monocyte cytokine production in response to *Leishmania* infection by influencing the innate and adaptive immune systems using parasitic virulence factors [22, 26, 30, 52, 54, 61]. Silverman and colleagues found that *L. donovani* exosomes could be predominantly immunosuppressive regarding cytokine responses on IFN-γ inhibition and IL-10 production by human moDCs [54]. In another study, macrophage-infected exosomes in naive macrophages were shown to downregulate the pro-inflammatory genes and suppression of macrophage activation [26]. Similarly, EVs secreted by the malaria parasite modulate the hosts' immune system to increase the survivability of the *Plasmodium* parasite. When parasites were blocked from secreting EVs, they had reduced virulence and lessened symptoms in models of cerebral malaria [93].

In addition to cytokine response, studies indicated that EVs can involve in the pathogenesis by modulating the microenvironment of the mammalian hosts which is at a high temperature and a low pH than the midgut of the sandfly and thus causing the disease [30, 61, 69]. Up-regulation of EV secretion induced by infection-like temperatures suggested that these vesicles were released into the extracellular environment, before the invasion of a host such as macrophage, neutrophil or DC occurs.

While EVs play such a multifaceted role in immunomodulation and disease development at protozoan diseases, the application potential of EVs as therapeutic agents or drug delivery vehicles in therapy or as a biomarker at diagnostics attracts the researchers' attention working on these fields. Considering their immunomodulatory effects, EVs could be potential vaccine candidates as components for infectious diseases [100–106] and the application of protozoan EVs in the clinic may be expected in the near future.

*The Role of Extracellular Vesicles in Immunomodulation and Pathogenesis of* Leishmania*… DOI: http://dx.doi.org/10.5772/intechopen.101682*
