Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview

Abstract

Recently, the interest in extracellular vesicles (EVs) released by pathogens like bacteria, fungi, and parasites has rapidly increased. Many of these pathogens actively modulate the immune responses of their host and there is accumulating evidence that pathogen-derived EV contribute to this process. The effects of pathogen-derived EV on the host immune system have been attributed to proteins, lipids, nucleic acids, and glycans contained in, or present on these EV. For example, toxins in bacterial EV can modulate pathogen clearance and antigen presentation, while EV-associated polysaccharides are potential vaccine targets because they induce protective immune responses. Furthermore, parasite EV-associated microRNA may increase parasite survival via host gene repression, and the lipid A moiety of LPS in bacteria-derived EV induces strong pro-inflammatory responses. Research on pathogen EV-associated molecules may pave new avenues to combat infectious diseases by immune intervention. This review provides an overview of the current knowledge of EV-associated molecules released by extracellular pathogens and their effects on the host immune system. The current focus and future hotspots of this rapidly expanding field will be highlighted and discussed.

Answers to naysayers regarding microbial extracellular vesicles

“…The same is found for RNA cargo, where RNA cargo does not reflect the RNA content of intact cells, which is highly suggestive of selective enrichment [31]. While EVs are enriched in proteins directed for secretion, namely secreted virulence factors (reviewed elsewhere [13]), direct comparison of cell-free and EV-depleted supernatant found that EV composition is only 30% similar to the EV-free supernatant in the fungi Paracoccidioides brasiliensis and Candida albicans [34,35]. Furthermore, experiments adding an extraneous component (easily detectable for high sensitivity) to actively growing bacteria showed no detection of this extraneous component in EVs [36], arguing against the self-aggregation of lipids entrapping the components of the media.…”

“…Magnetosomes, the organelles capable of detecting magnetic fields for spatial orientation in Magnetospirillum spp., are invaginations of the cellular membrane [20,21,25]. Intracellular vesicles have been observed by electron cryotomography in several genus of Gram-negative bacteria [13]. In some bacteria membranous structures extend outwards of the bacterial cell body.…”

“…EVs have been associated with pathogenicity from delivering toxins to the host as well as antibiotic resistance, partially by contributing to biofilm formation [11,12]. On the other hand, EVs have been harnessed for vaccines: EVs are protective as vaccines in mouse models for several human pathogens [13,14]. The potential of EVs as vaccines is sufficient to warrant detailed studies of EVs.…”

Co‐opting oxylipin signals in microbial disease

“…Where might the future directions microbial oxylipin research head? An increasing body of literature has reported that microbial extracellular vesicles modulate host immunological response (Joffe, Nimrichter, Rodrigues, & Del Poeta, ; Kuipers, Hokke, Smits, & Nolte‐'t Hoen, ). In mammalian systems, extracellular vesicles facilitate intercellular transport of eicosanoids and their biosynthetic machinery, mediating paracrine signalling (Boilard, ; Sagini, Costanzi, Emiliani, Buratta, & Urbanelli, ).…”

Inside-Out: From Endosomes to Extracellular Vesicles in Fungal RNA Transport

“…Already observed in early ultrastructural studies, EVs have only recently begun to gain increasing attention from plant scientists and microbiologists. EVs are proposed to play pivotal roles in cross-kingdom communication between microbial pathogensand their hosts(Bielska et al, 2019;Bielska and May, 2019;Kuipers et al, 2018;…”