Release of Small RNA-containing Exosome-like Vesicles from the Human Filarial Parasite Brugia malayi

M. Zamanian, L.M. Fraser, P.N. Agbedanu, H. Harischandra, A.R. Moorhead, T.A. Day, L.C. Bartholomay, M.J. Kimber

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Lymphatic filariasis (LF) is a socio-economically devastating mosquito-borne Neglected Tropical Disease caused by parasitic filarial nematodes. The interaction between the parasite and host, both mosquito and human, during infection, development and persistence is dynamic and delicately balanced. Manipulation of this interface to the detriment of the parasite is a promising potential avenue to develop disease therapies but is prevented by our very limited understanding of the host-parasite relationship. Exosomes are bioactive small vesicles (30–120 nm) secreted by a wide range of cell types and involved in a wide range of physiological processes. Here, we report the identification and partial characterization of exosome-like vesicles (ELVs) released from the infective L3 stage of the human filarial parasite Brugia malayi. Exosome-like vesicles were isolated from parasites in culture media and electron microscopy and nanoparticle tracking analysis were used to confirm that vesicles produced by juvenile B. malayi are exosome-like based on size and morphology. We show that loss of parasite viability correlates with a time-dependent decay in vesicle size specificity and rate of release. The protein cargo of these vesicles is shown to include common exosomal protein markers and putative effector proteins. These Brugia-derived vesicles contain small RNA species that include microRNAs with host homology, suggesting a potential role in host manipulation. Confocal microscopy shows J774A.1, a murine macrophage cell line, internalize purified ELVs, and we demonstrate that these ELVs effectively stimulate a classically activated macrophage phenotype in J774A.1. To our knowledge, this is the first report of exosome-like vesicle release by a human parasitic nematode and our data suggest a novel mechanism by which human parasitic nematodes may actively direct the host responses to infection. Further interrogation of the makeup and function of these bioactive vesicles could seed new therapeutic strategies and unearth stage-specific diagnostic biomarkers. © 2015 Zamanian et al.
Original languageEnglish
Article numbere0004069
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number9
DOIs
Publication statusPublished - 2015

Bibliographical note

cited By 35

Keywords

  • colony stimulating factor 1
  • eotaxin
  • gamma interferon
  • gamma interferon inducible protein 10
  • granulocyte colony stimulating factor
  • granulocyte macrophage colony stimulating factor
  • interleukin 10
  • interleukin 12
  • interleukin 13
  • interleukin 15
  • interleukin 17
  • interleukin 1alpha
  • interleukin 1beta
  • interleukin 2
  • interleukin 3
  • interleukin 4
  • interleukin 5
  • interleukin 6
  • interleukin 7
  • interleukin 9
  • leukemia inhibitory factor receptor
  • macrophage inflammatory protein 1alpha
  • macrophage inflammatory protein 1beta
  • microRNA
  • monocyte chemotactic protein 1
  • RANTES
  • small nuclear RNA
  • tumor necrosis factor alpha
  • unindexed drug
  • vasculotropin
  • helminth protein
  • small untranslated RNA, adult
  • animal experiment
  • animal tissue
  • Article
  • blood sampling
  • Brugia malayi
  • cell structure
  • cell tracking
  • cell vacuole
  • confocal microscopy
  • controlled study
  • exosome
  • female
  • gene sequence
  • immune response
  • liquid chromatography
  • macrophage
  • male
  • mass spectrometry
  • nonhuman
  • parasite viability
  • phenotype
  • proteomics
  • RNA binding
  • RNA isolation
  • transmission electron microscopy
  • animal
  • cell line
  • chemistry
  • electron microscopy
  • immunology
  • metabolism
  • phagocytosis
  • ultrastructure, Animals
  • Cell Line
  • Exosomes
  • Helminth Proteins
  • Macrophages
  • Microscopy, Electron
  • Phagocytosis
  • RNA, Small Untranslated

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