Emerging roles of extracellular vesicles in immunomodulation during host-pathogen interactions

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Background

Recently, cell-cell communication using extracellular vesicles (EVs) has drawn special interest among immunologists as they carry an array of immunostimulatory and/or immunosuppressive molecules either into the luminal space or to the cell surface. EVs are broadly divided into three main categories: apoptotic bodies, exosomes, and microvesicles that are released from pathogens and host cells during infection. EVs represent a mechanism of cell-to-cell communication through direct stimulation of cells by receptor-mediated contact and/or via transfer of proteins, lipids, and nucleic acids. During host-pathogen interaction, these vesicles deliver pathogen-derived molecules such as antigens or agonists of innate immune receptors that induce host defense and immunity, and virulence factors that mediate immune evasion. Recent studies have further demonstrated that intracellular pathogens exploit host EVs secretion/composition to manipulate immune response. Moreover, macrophages infected with intracellular pathogens like Mycobacterium tuberculosis, M bovis, Salmonella typhimurium or Toxoplasma gondii secrete exosomes containing pathogen-associated molecular patterns. Also, EV released from Plasmodium infected RBC have been reported to modulate host monocyte. Further, these exosomes can stimulate both CD4+ and CD8+ splenic T cells to secrete cytokines.

The detailed understanding of how pathogens influence EVs biogenesis in infected hosts and its overall importance of these host-secreted EVs in modulating crosstalk between different immune cells is ambiguous. Apart from playing a role in immunomodulation in different infectious diseases and in cancer, the potential of EVs in medical applications has also been exploited, by developing EV-based selective anti-inflammatory drug vehicles in different mouse models of inflammation. EVs have been employed as immunomodulators to treat severe forms of graft-versus-host disease in humans as well. Moreover, dendritic cell-secreted EVs pulsed with tumor antigens have been tested in clinical trials as tumor vaccines. Recent evidence also suggested that EVs may serve as biomarkers in various pathological conditions ranging from cancer to sepsis.
The field of EVs is emerging rapidly and we still have a lot to learn about their role in host-pathogen interaction to successfully employ them for therapeutic, prophylactic, and prognostic purposes.

We welcome the submission of Original Research, Systematic Review, Reviews, Mini-Reviews, Methods, Perspective, and Technology and Code articles that address, but are not limited to, the following topics:
• Mechanism of biogenesis and secretion of extracellular vesicle (EVs) from pathogen/infected host
• EVs released by various pathogens and their effects on the host immunity and in immunosuppression
• Role of EVs in modulating antigen presentation, immune cell polarization, T cell differentiation, immunotolerance and immune cell migration during infection
• Role of EVs in modulating immune cell crosstalk and signaling during infection
• EVs as biomarkers, therapeutic and prophylactic tools in infectious diseases.

Keywords: Exovesicles, infectious diseases, immunomodulation, biomarkers, immunotherapeutic, immunoprophylactic

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