Bacteria- and host-derived extracellular vesicles – two sides of the same coin?

Abstract

Intracellular bacterial pathogens spend portions of their life cycle both inside and outside host cells. While in these two distinct environments, they release or shed bacterial components, including virulence factors that promote their survival and replication. Some of these components are released through extracellular vesicles, which are either derived from the bacteria themselves or from the host cells. Bacteria- and host-derived vesicles have been studied almost exclusively in isolation from each other, with little discussion of the other type of secreted vesicles, despite the fact that both are generated during an in vivo infection and both are likely play a role in bacterial pathogenesis and host immunity. In this Review, we aim to bridge this gap and discuss what we know of bacterial membrane vesicles in their generation and composition. We will compare and contrast this with the composition of host-derived vesicles with regard to bacterial components. We will also compare host cell responses to the different vesicles, with a focus on how these vesicles modulate the immune response, using Mycobacterium, Listeria and Salmonella as specific examples for these comparisons.

Extracellular Vesicles in Mycobacteria and Tuberculosis

“…Authors from the ubiquination and Rab27a studies suggest that the conclusions reached by Athman et al (2015) were premature (Schorey et al, 2021). Schorey et al (2021) state that "this conclusion is based on the detection of LAM-positive vesicles lacking the exosomal markers CD9 and CD63; however recent data for exosomes and other [human] EVs indicate a significantly greater heterogeneity in vesicle composition than previously appreciated, with classic exosome markers such as CD9 and CD63 being present on only a subset of exosomes (Kowal et al, 2016)" (Schorey et al, 2021).…”

“…Authors from the ubiquination and Rab27a studies suggest that the conclusions reached by Athman et al (2015) were premature (Schorey et al, 2021). Schorey et al (2021) state that "this conclusion is based on the detection of LAM-positive vesicles lacking the exosomal markers CD9 and CD63; however recent data for exosomes and other [human] EVs indicate a significantly greater heterogeneity in vesicle composition than previously appreciated, with classic exosome markers such as CD9 and CD63 being present on only a subset of exosomes (Kowal et al, 2016)" (Schorey et al, 2021). In addition to exosome diversity regarding classical markers such as CD9 and CD63, it is important to note that The immunofluorescence microscopy labeling in the Athman et al study was performed with polyclonal anti-Mtb, which "detects LAM and LM, although its specificity is not limited to these lipoglycans" (Athman et al, 2015).…”

“…It is impossible to confirm complete separation of human and Mtb EVs based on the data provided. Further proteomic analysis of the density gradient-enriched populations, as suggested by Schorey et al (2021), would help answer this question (Schorey et al, 2021). The functions specifically attributed to mycobacterial EVs from mycobacterial culture verses EVs generated during in vitro or in vivo infection is provided in Figure 1.…”

Extracellular vesicles from helicobacter pylori‐infected cells and helicobacter pylori outer membrane vesicles in atherosclerosis

“…EVs not only involve various physiological processes but also involve pathological processes, especially pathogen infection. [72][73][74] After infection by a pathogen, the EVs released from host cells may change in composition, and carry pathogenic components (e.g., proteins, lipids, nucleic acids, and carbohydrates) to the surrounding cells and tissues. Since EVs are a nanocarrier of molecules from pathogens and pathogen-infected cells, González and colleagues proposed a hypothesis that EVs released from H. pylori-infected gastric epithelial cells can enter the blood and reach other tissues, resulting in extragastric diseases.…”

“…EVs transfer their content from donor cells to recipient cells and play the autocrine/paracrine role in cell–cell communication. EVs not only involve various physiological processes but also involve pathological processes, especially pathogen infection 72‐74 . After infection by a pathogen, the EVs released from host cells may change in composition, and carry pathogenic components (e.g., proteins, lipids, nucleic acids, and carbohydrates) to the surrounding cells and tissues.…”