Abstract
The extracellular vesicles (EVs) released by Leishmania can contribute to the establishment of infection and host immunomodulation. In this study, we characterized the shedding of EVs from Leishmania (Leishmania) amazonensis promastigotes. This species is the causative agent of cutaneous leishmaniasis, and its role during interactions with bone marrow-derived macrophages (BMDMs) and peritoneal B-1 cells was evaluated. Leishmania amazonensis promastigotes cultivated in vitro at different times and temperatures spontaneously released EVs. EVs were purified using size-exclusion chromatography (SEC) and quantitated by nanoparticle tracking analysis (NTA). NTA revealed that the average size of the EVs was approximately 180 nm, with concentrations ranging from 1.8 × 108 to 2.4 × 109 vesicles/mL. In addition, the presence of LPG and GP63 were detected in EVs obtained at different temperatures. Naïve BMDMs stimulated with EVs exhibited increased IL-10 and IL-6 expression. However, incubating B-1 cells with parasite EVs did not stimulate IL-10 expression but led to an increase in the expression of IL-6 and TNFα. After 7 weeks post-infection, animals infected with L. amazonensis promastigotes in the presence of parasite EVs had significant higher parasite load and a polarization to Th2 response, as compared to the group infected with the parasite alone. This work demonstrated that EVs isolated from L. amazonensis promastigotes were able to stimulate macrophages and B-1 cells to express different types of cytokines. Moreover, the immunomodulatory properties of EVs probably contributed to an increase in parasite burden in mice. These findings suggest that the functionality of L. amazonensis EVs on immune system favor of parasite survival and disease progression.
Highlights
Extracellular vesicles (EVs) are a heterogeneous group of particles that are released by cells and play a pivotal role in intercellular communication (Théry et al, 2006)
Extracellular vesicles were successfully released by L. amazonensis promastigotes following scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA) analysis
Microscopy confirmed that extracellular vesicles (EVs) release occurred throughout the whole body at all times and temperatures analyzed (Figure 1 and Supplementary Figure S2)
Summary
Extracellular vesicles (EVs) are a heterogeneous group of particles that are released by cells and play a pivotal role in intercellular communication (Théry et al, 2006). Intercellular communication by EVs can be carried out within the same species or between different species (Szempruch et al, 2016; Sampaio et al, 2018). Studies with pathogenic protozoa have demonstrated that EVs released by these parasites play an important role in their survival at different levels, such as facilitating infection in experimental models (Martin-Jaular et al, 2011; Nogueira et al, 2015), immunomodulation (Coakley et al, 2017), adaptation of the parasite to the host environment (Lambertz et al, 2012) and the transfer of resistance factors to drugs (Regev-Rudzki et al, 2013; Szempruch et al, 2016; Sampaio et al, 2018). The EVs released by some pathogens can mediate both parasite-parasite (Szempruch et al, 2016) and parasite-host (Nogueira et al, 2015; Soares et al, 2017) intercellular communication
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