Abstract
The study of host–pathogen interactions has increased considerably in recent decades. This intercellular communication has been mediated by extracellular vesicles (EVs) that play an ...important role during the interaction. EVs are particles of lipid bilayer and described in different types of cells, eukaryotic or prokaryotic. Depending on their biogenesis they are described as exosomes (derived from multivesicular bodies) and microvesicles (derived from the plasma membrane). The EVs carry biomolecules, including nucleic acids, lipids, and proteins that can be released or internalized by other cells in different pathways (endocytosis, macropinocytosis, phagocytosis, or membrane fusion) in the process described as uptake. The balance between biogenesis and uptake of EVs could modify physiological and pathophysiological processes of the cell. This review is focusing on the dynamic roles of release and capture of EVs during host–pathogen interaction. We also do a critical analysis of methodologies for obtaining and analyzing EVs. Finally, we draw attention to critical points to be considered in EV biogenesis and uptake studies.
The innate immune system is the first mechanism of vertebrate defense against pathogen infection. In this study, we present evidence for a novel immune evasion mechanism of Trypanosoma cruzi, ...mediated by host cell plasma membrane-derived vesicles. We found that T. cruzi metacyclic trypomastigotes induced microvesicle release from blood cells early in infection. Upon their release, microvesicles formed a complex on the T. cruzi surface with the complement C3 convertase, leading to its stabilization and inhibition, and ultimately resulting in increased parasite survival. Furthermore, we found that TGF-β-bearing microvesicles released from monocytes and lymphocytes promoted rapid cell invasion by T. cruzi, which also contributed to parasites escaping the complement attack. In addition, in vivo infection with T. cruzi showed a rapid increase of microvesicle levels in mouse plasma, and infection with exogenous microvesicles resulted in increased T. cruzi parasitemia. Altogether, these data support a role for microvesicles contributing to T. cruzi evasion of innate immunity.
•Different anaerobic protozoans release extracellular vesicles (EVs).•Protozoa produce EVs that modulate host-parasite interaction.•EVs contribute to pathogenesis of diseases caused by ...anaerobic.•Anaerobic EVs analysis by proteomics help to understand communication intercellular.
The anaerobic or microaerophilic protozoan parasites such as the enteric human pathogens Entamoeba histolytica, Giardia intestinalis, Cryptosporidium parvum, Blastocystis hominis and urogenital tract parasites Trichomonas vaginalis are able to survival in an environment with oxygen deprivation. Despite living in hostile environments these pathogens adopted different strategies to survive within the hosts. Among them, the release of extracellular vesicles (EVs) has become an active endeavor in the study of pathogenesis for these parasites. EVs are heterogenous, membrane-limited structures that have played important roles in cellular communication, transferring information through cargo and modulating the immune system of the host. In this review, we described several aspects of the recently characterized EVs of the anaerobic protozoa, including their role in adhesion, modulation of the immune response and omics analysis to understand the potential of these EVs in the pathogenesis of these diseases caused by anaerobic parasites.
Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. ...These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review.
The complement system is the main arm of the vertebrate innate immune system against pathogen infection. For the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, subverting the ...complement system and invading the host cells is crucial to succeed in infection. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. To address this question, we decided to analyse: 1) which complement pathways are activated by T. cruzi using strains isolated from different hosts, 2) the capacity of these strains to resist the complement-mediated killing at nearly physiological conditions, and 3) whether the complement system could limit or control T. cruzi invasion of eukaryotic cells. The complement activating molecules C1q, C3, mannan-binding lectin and ficolins bound to all strains analysed; however, C3b and C4b deposition assays revealed that T. cruzi activates mainly the lectin and alternative complement pathways in non-immune human serum. Strikingly, we detected that metacyclic trypomastigotes of some T. cruzi strains were highly susceptible to complement-mediated killing in non-immune serum, while other strains were resistant. Furthermore, the rate of parasite invasion in eukaryotic cells was decreased by non-immune serum. Altogether, these results establish that the complement system recognizes T. cruzi metacyclic trypomastigotes, resulting in killing of susceptible strains. The complement system, therefore, acts as a physiological barrier which resistant strains have to evade for successful host infection.
Parasite-host cell interaction can be modulated by a dynamic communication between extracellular vesicles (EVs). They should play key roles in cell-cell communications transferring biomolecules ...(miRNA, proteins, soluble factors) from one cell to another cell. While many names have been used to denominate EVs, a better comprehension to understand these vesicles is raised when we classify it according to biogenesis: originated from multivesicular bodies, named exosomes, and from plasmatic membranes, denominated microvesicles. Here, we have reviewed EV participation during the protozoan-host cell interaction and reinforced the differences and similarities between exosomes and microvesicles, suggesting different intracellular routes and functions. We also discussed perspectives to study EVs and the role of EVs in diagnosis and chemotherapies of infectious diseases.
Trichomonas vaginalis
is a common sexually transmitted extracellular parasite that adheres to epithelial cells in the human urogenital tract. Extracellular vesicles (EVs) have been described as ...important players in the pathogenesis of this parasite as they deliver proteins and RNA into host cells and modulate parasite adherence. EVs are heterogeneous membrane vesicles released from virtually all cell types that collectively represent a new dimension of intercellular communication. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery contributes to several key mechanisms in which it reshapes membranes. Based on this, some components of the ESCRT have been implicated in EVs biogenesis in other cells. Here, we demonstrated that VPS32, a member of ESCRTIII complex, contribute to the biogenesis and cargo sorting of extracellular vesicles in the parasite
T. vaginalis.
Moreover, we observe that parasites overexpressing VPS32 have a striking increase in adherence to host cells compared to control parasites; demonstrating a key role for this protein in mediating host: parasite interactions. These results provide valuable information on the molecular mechanisms involved in extracellular vesicles biogenesis, cargo-sorting, and parasite pathogenesis.
In an academic semester, living in social isolation and under restrictions of the pandemic, we organized weekly multidisciplinary seminars from a postgraduate course program in Curitiba, Southern ...Brazil, integrating students from different regions of Brazil and South America. Outstanding researchers from Brazil, Germany, France, Argentina, Mexico, Portugal, England, and United States’ institutions gave seminars on chronic and infectious diseases with immunological, pharmacological, biochemical, cellular, and molecular biology point of views. The meetings were longer than traditional seminars, containing a part with scientific debate and other with a humanization or deconstruction of the researcher including trajectory, hobbies, scientific, and social thoughts. To facilitate learning and conceptualization, the seminars were available through YouTube and we applied weekly questionnaires to be answered rescuing scientific and motivational topics to give companionship and support to the students in pandemic times. Here, we are defending the creation of permanent platforms for scientific diffusion, with higher accessibility, connecting centers of different levels and giving academic excellence and opportunities for young researchers. Feedback received from participants indicates that this seminar structure can increase confidence and improve their perception of scientific processes and inspire researchers with development trajectories. We have discussed multidisciplinarity, scientific excellence, regional isolation and economic inequality, integration, humanization, and the value of science in society.
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