The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1β secretion in macrophages

Int J Parasitol. 2015 Nov;45(13):809-13. doi: 10.1016/j.ijpara.2015.08.005. Epub 2015 Sep 16.

Abstract

The T2 ribonuclease omega-1 is a powerful Th2-inducing factor secreted by the eggs of the blood fluke Schistosoma mansoni. Omega-1 can modulate pattern recognition receptor-induced inflammatory signatures and alter antigen presentation by dendritic cells. Recent findings have suggested that component(s) contained in or secreted by S. mansoni eggs (soluble egg antigen) can also enhance IL-1β secretion by dendritic cells stimulated with pattern recognition receptor ligands. Here we show that omega-1 enhances IL-1β secretion in macrophages stimulated with Toll-like receptor 2 ligand, and propose omega-1 as the factor in soluble egg antigen capable of regulating inflammasome activity. This effect is dependent on the C-type lectin receptor Dectin-1, caspase-8 and the ASC inflammasome adaptor protein, highlighting the ability of omega-1 to regulate multiple pattern recognition receptor signalling pathways. These mechanistic insights into manipulation of host immunity by a parasite product have implications for the design of anti-inflammatory therapeutic drugs.

Keywords: IL-1β; IPSE/alpha-1; Inflammasome; Omega-1; Schistosoma mansoni antigens; T2 ribonuclease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / metabolism*
  • Caspase 8 / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Egg Proteins / metabolism*
  • Endoribonucleases / immunology*
  • Endoribonucleases / metabolism
  • Humans
  • Inflammasomes / immunology*
  • Inflammasomes / metabolism
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / metabolism
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Schistosoma mansoni / enzymology
  • Schistosoma mansoni / immunology*
  • Th2 Cells / immunology

Substances

  • Antigens, Helminth
  • Egg Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lectins, C-Type
  • dectin 1
  • omega-1 antigen, Schistosoma mansoni
  • Endoribonucleases
  • ribonuclease T(2)
  • Caspase 8