Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite–host cross talk

Abstract

The prevalent porcine helminth, Ascaris suum, compromises pig health and reduces farm productivity worldwide. The closely related human parasite, A. lumbricoides, infects more than 800 million people representing a disease burden of 1.31 million disability-adjusted life years. The infections are often chronic in nature, and the parasites have a profound ability to modulate their hosts' immune responses. This study provides the first in-depth characterisation of extracellular vesicles (EVs) from different developmental stages and body parts of A. suum and proposes the role of these vesicles in the host-parasite interplay. The release of EVs from the third-(L3) and fourth-stage (L4) larvae and adults was demonstrated by transmission electron microscopy (TEM), and sequencing of EV-derived RNA identified a number of microRNAs (miRNAs) and transcripts of potential host immune targets, such as IL-13, IL-25 and IL-33, were identified. Furthermore, proteomics of EVs identified several proteins with immunomodulatory properties and other proteins previously shown to be associated with parasite EVs. Taken together, these results suggest that A. suum EVs and their cargo may play a role in host-parasite interactions. This knowledge may pave the way to novel strategies for helminth infection control and knowledge of their immune modulatory potential.

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

“…The cargo of B. malayi EVs includes proteins and miRNAs that have immunomodulatory functions and include modulatory proteins such as galectins and MIF-1 as well as miRNAs with identity to immunomodulatory host miRNAs (Harischandra et al, 2018;Zamanian et al, 2015). EVs from other nematode species are similarly imbued; protein and small RNA profiling of EV cargo from a range of gastrointestinal and filarial nematodes reveals a multitude of putative effector molecules with emerging functionality at the host-parasite interface (Buck et al, 2014;Eichenberger, Ryan, et al, 2018;Eichenberger, Talukder, et al, 2018;Gu et al, 2017;Hansen et al, 2015Hansen et al, , 2019Shears et al, 2018;Tritten et al, 2017). It is reasonable to posit that specifically inhibiting EV secretion would obstruct the immunomodulatory capabilities of these parasites.…”

“…Consistent with a role in cell-to-cell communication, EVs contain diverse functional cargo that varies depending on the cellular origin of the EVs, but in general include bioactive proteins, RNA and lipids (Thery et al, 2002;Valadi et al, 2007). EV secretion from diverse parasitic nematodes has been described (Buck et al, 2014;Coakley et al, 2017;Eichenberger, Ryan, et al, 2018;Eichenberger, Talukder, et al, 2018;Gu et al, 2017;Hansen et al, 2015Hansen et al, , 2019Harischandra et al, 2018;Shears et al, 2018;Tritten et al, 2017;Tzelos et al, 2016;Zamanian et al, 2015) and the cargo of these EVs have immunomodulatory functions (Buck et al, 2014;Quintana et al, 2017;Tritten et al, 2016). We have previously reported that B. malayi secretes EVs and that their cargo has putative immunomodulatory properties (Harischandra et al, 2018;Zamanian et al, 2015).…”

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

“…Additionally, H. polygyrus vesicles have been demonstrated to be taken up by host macrophages, resulting in a downregulation of ST2, inhibiting their ability to function effectively as protective M2s (Coakley et al, 2017). Extracellular vesicles released by the porcine helminth Ascaris suum have also been identified as possessing numerous miRNA transcripts which likely target IL-13, IL-25 and IL-33 (Hansen et al, 2019). However, it is important to note that in the context of helminth infection, host-parasite interactions may vary widely dependent upon the specific helminth.…”

“…Increased IL-33 is detected in serum from L. donovani patients Rostan et al, 2013;Takele et al, 2016 ST2 deficient mice demonstrate an ability to control parasite burden and reduced hepatomegaly and splenomegaly in an L. infantum model Khalid et al, 2017 Helminth Infection Helminth activity causes an increase in IL-33 mRNA expression Andronicos et al, 2012 Hymenolupis diminuta infection of mice deficient in mast cells have reduced IL-33 associated with increased parasite burden Hepworth et al, 2012;González et al, 2018 Mice pre-sensitized to an allergen prior to Ascaris lumbricoides infection demonstrate singificantly enhanced IL-33 expression and decreased parasite burden Gazzinelli-Guimaraes et al, 2019 IL-33 deficient mice cannot effectively recruit eosinophils or induce goblet cell hyperplasia Yasuda et al, 2012 IL-33 deficient mice cannot effectively recruit ILC2 cells resulting in increased parasite burden Yasuda et al, 2012Yasuda et al, , 2018 Heligmosomoides polygyrus exosomes inhibit IL-33/ST2 and M2 differentiation Buck et al, 2014;McSorley et al, 2014;Coakley et al, 2017 Ascaris suum exosomes likely inhibit IL-33 Hansen et al, 2019 Fasciola hepatica exosomes demonstrate an upregulation of IL-33 Finlay et al, 2016 combined with poor disease management practices, drug toxicity and a rise in parasitic resistance, have resulted in the high incidence and prevalence of parasitic infections seen in both developing and developed countries alike (Singh et al, 2019). For many years the scientific community has been working on developing novel strategies to prevent, contain and combat parasitic diseases.…”

Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

“…EVs are membrane-bound organelles released by cells that can act as mediators of intercellular communication by transferring molecular signals mediated by proteins, lipids, metabolites, mRNAs, microRNAs and other non-coding RNA species [23,24]. In addition to the transmission of information between cells within the same organism, recent studies have shown that EVs secreted by parasitic helminths are taken up by host cells within the parasite’s niche tissue and provide a means of inter-species communication [19,25-38]. For instance, EVs from trematodes and nematodes can be internalised by host cells whereupon they suppress effector immune responses [37,39,40], or in contrast, some helminth EVs contribute to pathogenesis by promoting cell proliferation and inflammatory cytokine production [29].…”