L4 stage Heligmosomoides polygyrus prevents the maturation of dendritic JAWS II cells

Exp Parasitol. 2019 Jan:196:12-21. doi: 10.1016/j.exppara.2018.10.010. Epub 2018 Nov 19.

Abstract

Helminths and their products are strong candidates for the treatment of autoimmunological disorders and allergies. Being a key population of antigen-presenting cells, dendritic cells play a crucial role in the therapeutic potential of worms. The study compares the effects of live pre-male and pre-female L4 stage Heligmosomoides polygyrus administration on the maturation and activation of the JAWS II line of immature dendritic cells. On stimulation with L4 stage H. polygyrus, JAWS II cells acquire semi-mature status and induce Th2 and regulatory responses in vitro. The strongest immunosuppressive effect on JAWS II cells was observed following stimulation with both sexes of nematodes together; this was manifested as immature dendritic cell morphology, proliferation inhibition, cell cycle change, decreased translocation of NF-κB into the nucleus, and lower expression of surface cellular costimulatory molecules CD80, CD86 and MHC I. However, greater production of proinflammatory (IL-12p70, TNF-α, IL-6) and Th2 response-promoting cytokines (IL-4) was observed by JAWS II following exposure to both sexes compared to male or female larvae alone. Sex had no influence on the viability, apoptosis process or endocytosis abilities of the JAWS II cell line. The findings indicate that the presence of only a single sex of the parasite influences a developed response, resulting in reduced proinflammatory and an antiparasitic reaction.

Keywords: Dendritic cells; Heligmosomoides polygyrus; Immunomodulation; JAWS II line cells; L4 stage.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / parasitology
  • Bone Marrow Cells / physiology
  • Cell Cycle
  • Cell Line
  • Chemokines / analysis
  • Cytokines / analysis
  • Dendritic Cells / immunology
  • Dendritic Cells / parasitology*
  • Dendritic Cells / physiology
  • Endocytosis
  • Female
  • Larva / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / analysis
  • Nematospiroides dubius / growth & development
  • Nematospiroides dubius / physiology*
  • Sex Factors
  • Specific Pathogen-Free Organisms

Substances

  • Chemokines
  • Cytokines
  • NF-kappa B