The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis

James Doonan, Anuradha Tarafdar, Miguel A. Pineda, Felicity E. Lumb, Jenny Crowe, Aneesah M. Khan, Paul A. Hoskisson, Margaret M. Harnett, William Harnett

Research output: Contribution to journalArticle

11 Citations (Scopus)
13 Downloads (Pure)

Abstract

The human immune system has evolved in the context of our colonisation by bacteria, viruses, fungi and parasitic helminths. Reflecting this, the rapid eradication of pathogens appears to have resulted in reduced microbiome diversity and generation of chronically activated immune systems, presaging the recent rise of allergic, autoimmune and metabolic disorders. Certainly, gastrointestinal helminths can protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Here, we employ ES-62, an immunomodulator secreted by tissue-dwelling Acanthocheilonema viteae to show that helminth-modulation of the gut microbiome does not require live infection with gastrointestinal-based worms nor is protection restricted to mucosal diseases. Specifically, subcutaneous administration of this defined immunomodulator affords protection against joint disease in collagen-induced arthritis, a mouse model of rheumatoid arthritis, which is associated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity.
Original languageEnglish
Article number1554
Number of pages14
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 5 Apr 2019

Keywords

  • human immune system
  • inflammatory conditions
  • rheumatoid arthritis
  • ES-62
  • parasitic worm

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