Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: Implications for exosome stability and biology

Fabio Simbari, Jana McCaskill, Gillian Coakley, Marissa Millar, Rick M. Maizels, Gemma Fabri�s, Josefina Casas, Amy H. Buck

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically diverse species and can be used by parasites to alter the properties of the host environment.Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be diverse based on the physiology and environmental niche of different organisms.Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we termexosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those fromthe nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs,which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on diversity in the molecular properties of EVs that enable them to function in cross-species communication.

Original languageEnglish
Article number30741
Number of pages17
JournalJournal of Extracellular Vesicles
Volume5
Issue number1
DOIs
Publication statusPublished - 2016

Keywords

  • Cholesterol
  • Cross-species communication
  • Dynamic light scattering
  • Ether lipids
  • Extracellular vesicles
  • Helminth
  • Host-pathogen

Cite this

Simbari, Fabio ; McCaskill, Jana ; Coakley, Gillian ; Millar, Marissa ; Maizels, Rick M. ; Fabri�s, Gemma ; Casas, Josefina ; Buck, Amy H. / Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host : Implications for exosome stability and biology. In: Journal of Extracellular Vesicles. 2016 ; Vol. 5, No. 1.
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Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host : Implications for exosome stability and biology. / Simbari, Fabio; McCaskill, Jana; Coakley, Gillian; Millar, Marissa; Maizels, Rick M.; Fabri�s, Gemma; Casas, Josefina; Buck, Amy H.

In: Journal of Extracellular Vesicles, Vol. 5, No. 1, 30741, 2016.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - Implications for exosome stability and biology

AU - Simbari, Fabio

AU - McCaskill, Jana

AU - Coakley, Gillian

AU - Millar, Marissa

AU - Maizels, Rick M.

AU - Fabri�s, Gemma

AU - Casas, Josefina

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