scholarly journals Extracellular Vesicles Released by Leishmania: Impact on Disease Development and Immune System Cells

2021 ◽  
Author(s):  
Rogéria Cristina Zauli ◽  
Andrey Sladkevicius Vidal ◽  
Talita Vieira Dupin ◽  
Aline Correia Costa de Morais ◽  
Wagner Luiz Batista ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Immune Cells ◽  
Diagnostic Tool ◽  
Experimental Models ◽  
Host Cells ◽  
Disease Development ◽  
Leishmania Spp

Leishmania spp. release extracellular vesicles (EVs) containing parasite molecules, including several antigens and virulence factors. These EVs can interact with the host cells, such as immune cells, contributing to the parasite–host relationship. Studies have demonstrated that Leishmania-EVs can promote infection in experimental models and modulate the immune response. Although the immunomodulatory effect has been demonstrated, Leishmania-EVs can deliver parasite antigens and therefore have the potential for use as a new diagnostic tool and development of new therapeutic and vaccine approaches. This review aims to bring significant advances in the field of extracellular vesicles and Leishmania, focusing on their role in the cells of the immune system.

scholarly journals Extracellular Vesicles: Potential Role in Remote Signaling and Inflammation in Trypanosoma cruzi-Triggered Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Rubem Menna-Barreto ◽  
Joseli Lannes-Vieira
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Chronic Phase ◽  
Signs And Symptoms ◽  
Experimental Models ◽  
Host Cells ◽  
Low Grade ◽  
Cell Infection

Extracellular vesicles (EVs) act as cell communicators and immune response modulators and may be employed as disease biomarkers and drug delivery systems. In infectious diseases, EVs can be released by the pathogen itself or by the host cells (infected or uninfected), potentially impacting the outcome of the immune response and pathological processes. Chagas disease (CD) is caused by infection by the protozoan Trypanosoma cruzi and is the main cause of heart failure in endemic areas. This illness attracted worldwide attention due to the presence of symptomatic seropositive subjects in North America, Asia, Oceania, and Europe. In the acute phase of infection, nonspecific signs, and symptoms contribute to miss diagnosis and early etiological treatment. In this phase, the immune response is crucial for parasite control; however, parasite persistence, dysregulated immune response, and intrinsic tissue factors may contribute to the pathogenesis of chronic CD. Most seropositive subjects remain in the indeterminate chronic form, and from 30 to 40% of the subjects develop cardiac, digestive, or cardio-digestive manifestations. Identification of EVs containing T. cruzi antigens suggests that these vesicles may target host cells and regulate cellular processes and the immune response by molecular mechanisms that remain to be determined. Parasite-released EVs modulate the host-parasite interplay, stimulate intracellular parasite differentiation and survival, and promote a regulatory cytokine profile in experimental models of CD. EVs derived from the parasite-cell interaction inhibit complement-mediated parasite lysis, allowing evasion. EVs released by T. cruzi-infected cells also regulate surrounding cells, maintaining a proinflammatory profile. After a brief review of the basic features of EVs, the present study focuses on potential participation of T. cruzi-secreted EVs in cell infection and persistence of low-grade parasite load in the chronic phase of infection. We also discuss the role of EVs in shaping the host immune response and in pathogenesis and progression of CD.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1530
Author(s):  
Alfonso Olaya-Abril ◽  
Rafael Prados-Rosales ◽  
José A. González-Reyes ◽  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Activity ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Pneumococcal Serotypes ◽  
Human Pathogen ◽  
Host Immune Responses ◽  
Serotype 1 ◽  
Transient Loss

Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes.

scholarly journals Leishmania donovani Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tanvir Bamra ◽  
Taj Shafi ◽  
Sushmita Das ◽  
Manjay Kumar ◽  
Manas Ranjan Dikhit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Leishmania Donovani ◽  
Indian Subcontinent ◽  
Parasite Burden ◽  
Host Immune Response ◽  
Host Cells ◽  
Interleukin 4 ◽  
Host Immune System ◽  
Mevalonate Kinase

Summary StatementLeishmania secretes over 151 proteins during in vitro cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in Leishmania infection.Visceral Leishmaniasis is a persistent infection, caused by Leishmania donovani in Indian subcontinent. This persistence is partly due to phagocytosis and evasion of host immune response. The underlying mechanism involves secretory proteins of Leishmania parasite; however, related studies are meagre. We have identified a novel secretory Leishmania donovani glycoprotein, Mevalonate kinase (MVK), and shown its importance in parasite internalization and immuno-modulation. In our studies, MVK was found to be secreted maximum after 1 h temperature stress at 37°C. Its secretion was increased by 6.5-fold in phagolysosome-like condition (pH ~5.5, 37°C) than at pH ~7.4 and 25°C. Treatment with MVK modulated host immune system by inducing interleukin-10 and interleukin-4 secretion, suppressing host’s ability to kill the parasite. Peripheral blood mononuclear cell (PBMC)-derived macrophages infected with mevalonate kinase-overexpressing parasites showed an increase in intracellular parasite burden in comparison to infection with vector control parasites. Mechanism behind the increase in phagocytosis and immunosuppression was found to be phosphorylation of mitogen-activated protein (MAP) kinase pathway protein, Extracellular signal-regulated kinases-1/2, and actin scaffold protein, cortactin. Thus, we conclude that Leishmania donovani Mevalonate kinase aids in parasite engulfment and subvert the immune system by interfering with signal transduction pathways in host cells, which causes suppression of the protective response and facilitates their persistence in the host. Our work elucidates the involvement of Leishmania in the process of phagocytosis which is thought to be dependent largely on macrophages and contributes towards better understanding of host pathogen interactions.

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

scholarly journals The complex, bidirectional role of extracellular vesicles in infection

2021 ◽  
Author(s):  
Joni Renee White ◽  
Priscila Dauros-Singorenko ◽  
Jiwon Hong ◽  
Frédérique Vanholsbeeck ◽  
Anthony Phillips ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Bacterial Pathogens ◽  
Host Cells ◽  
Signalling Molecules ◽  
Host Pathogen ◽  
Domains Of Life

Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.

scholarly journals Nucleic Acid Nanoparticles at a Crossroads of Vaccines and Immunotherapies

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4620 ◽  
Author(s):  
Marina A. Dobrovolskaia
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nucleic Acid ◽  
Tobacco Smoke ◽  
Targeted Delivery ◽  
Host Cells ◽  
Antigen Delivery ◽  
Food Protein ◽  
Common Goal ◽  
Routes Of Administration

Vaccines and immunotherapies involve a variety of technologies and act through different mechanisms to achieve a common goal, which is to optimize the immune response against an antigen. The antigen could be a molecule expressed on a pathogen (e.g., a disease-causing bacterium, a virus or another microorganism), abnormal or damaged host cells (e.g., cancer cells), environmental agent (e.g., nicotine from a tobacco smoke), or an allergen (e.g., pollen or food protein). Immunogenic vaccines and therapies optimize the immune response to improve the eradication of the pathogen or damaged cells. In contrast, tolerogenic vaccines and therapies retrain or blunt the immune response to antigens, which are recognized by the immune system as harmful to the host. To optimize the immune response to either improve the immunogenicity or induce tolerance, researchers employ different routes of administration, antigen-delivery systems, and adjuvants. Nanocarriers and adjuvants are of particular interest to the fields of vaccines and immunotherapy as they allow for targeted delivery of the antigens and direct the immune response against these antigens in desirable direction (i.e., to either enhance immunogenicity or induce tolerance). Recently, nanoparticles gained particular attention as antigen carriers and adjuvants. This review focuses on a particular subclass of nanoparticles, which are made of nucleic acids, so-called nucleic acid nanoparticles or NANPs. Immunological properties of these novel materials and considerations for their clinical translation are discussed.

Elucidating the interaction dynamics between microswimmer body and immune system for medical microrobots

2020 ◽  
Vol 5 (43) ◽  
pp. eaaz3867 ◽  
Author(s):  
Immihan Ceren Yasa ◽  
Hakan Ceylan ◽  
Ugur Bozuyuk ◽  
Anna-Maria Wild ◽  
Metin Sitti
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cells ◽  
Structural Design ◽  
Design Parameters ◽  
Mouse Macrophage ◽  
Macrophage Cell ◽  
Interaction Dynamics ◽  
Physical Interactions ◽  
Surface Chemistries

The structural design parameters of a medical microrobot, such as the morphology and surface chemistry, should aim to minimize any physical interactions with the cells of the immune system. However, the same surface-borne design parameters are also critical for the locomotion performance of the microrobots. Understanding the interplay of such parameters targeting high locomotion performance and low immunogenicity at the same time is of paramount importance yet has so far been overlooked. Here, we investigated the interactions of magnetically steerable double-helical microswimmers with mouse macrophage cell lines and splenocytes, freshly harvested from mouse spleens, by systematically changing their helical morphology. We found that the macrophages and splenocytes can recognize and differentially elicit an immune response to helix turn numbers of the microswimmers that otherwise have the same size, bulk physical properties, and surface chemistries. Our findings suggest that the structural optimization of medical microrobots for the locomotion performance and interactions with the immune cells should be considered simultaneously because they are highly entangled and can demand a substantial design compromise from one another. Furthermore, we show that morphology-dependent interactions between macrophages and microswimmers can further present engineering opportunities for biohybrid microrobot designs. We demonstrate immunobots that can combine the steerable mobility of synthetic microswimmers and the immunoregulatory capability of macrophages for potential targeted immunotherapeutic applications.

scholarly journals Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

2020 ◽  
Vol 9 (4) ◽  
pp. 1185 ◽  
Author(s):  
Martha Baydoun ◽  
Olivier Moralès ◽  
Céline Frochot ◽  
Colombeau Ludovic ◽  
Bertrand Leroux ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Surgical Techniques ◽  
Ovarian Cancer Cells ◽  
The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

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