Abstract
To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.
Highlights
Cell-to-cell communication is essential to maintain homeostasis in a multicellular organism.Exosomes, small extracellular vesicles of 30 to 100 nm produced by most cell types and delivered into bodily fluids, are a part of a larger network by which cells communicate with each other [1].These vesicles arise from a unique biogenesis pathway starting with the inward budding of the plasma membrane to form membrane-enclosed compartment called early endosomes [2]
Exosomes from dendritic cells induce the activation and proliferation of natural killer (NK) cells via the IL-15Rα receptor on the exosomal surface that binds to IL-15, and via the UL16 binding protein 1 (ULBP1), a ligand for the natural killer group 2 member D (NKG2D) receptor expressed by NK cells [62]
Mesenchymal stem cell (MSC)-derived extracellular vesicles, including exosomes and microparticles, decrease the severity of TNBS-induced colitis in rats by suppressing activation of the NF-κB pathway [110], an effect probably mediated by the inhibition of TNF receptor associated factor 6 (TRAF6) and IL-1 receptor associated kinase 1 (IRAK1) by the anti-inflammatory miR-146a carried by these exosomes [111]
Summary
Cell-to-cell communication is essential to maintain homeostasis in a multicellular organism. In the context of infection with other pathogens, such as Salmonella enterica serovar Typhimurium, Toxoplasma gondii, Mycobacterium tuberculosis or Mycobacterium bovis, it has been reported that exosomes secreted by infected cells contain bacterial antigens [21,22,23], as well as bacteria- and host-derived nucleic acids [24,25,26], and modulate immune responses of uninfected surrounding cells [21,22,23,24,26,27] Due to their presence and high stability in most bodily fluids as well as the variation in their content in pathological conditions, exosomes have great potential to serve as biomarkers [28]. This review presents the advanced knowledge of exosome functions in bacterial infection and IBD and highlights their potential role as diagnostic biomarkers and vaccines as well as conveyers of therapeutic molecules
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