Trichuris suis induces human non-classical patrolling monocytes via the mannose receptor and PKC: implications for multiple sclerosis

Acta Neuropathol Commun. 2015 Jul 25;3:45. doi: 10.1186/s40478-015-0223-1.

Abstract

Introduction: The inverse correlation between prevalence of auto-immune disorders like the chronic neuro-inflammatory disease multiple sclerosis (MS) and the occurrence of helminth (worm) infections, suggests that the helminth-trained immune system is protective against auto-immunity. As monocytes are regarded as crucial players in the pathogenesis of auto-immune diseases, we explored the hypothesis that these innate effector cells are prime targets for helminths to exert their immunomodulatory effects.

Results: Here we show that soluble products of the porcine nematode Trichuris suis (TsSP) are potent in changing the phenotype and function of human monocytes by skewing classical monocytes into anti-inflammatory patrolling cells, which exhibit reduced trans-endothelial migration capacity in an in vitro model of the blood-brain barrier. Mechanistically, we identified the mannose receptor as the TsSP-interacting monocyte receptor and we revealed that specific downstream signalling occurs via protein kinase C (PKC), and in particular PKCδ.

Conclusion: This study provides comprehensive mechanistic insight into helminth-induced immunomodulation, which can be therapeutically exploited to combat various auto-immune disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Movement / physiology
  • Cytokines / metabolism
  • Flow Cytometry
  • Humans
  • Inflammation / parasitology*
  • Inflammation / pathology
  • Lectins, C-Type / metabolism*
  • Mannose-Binding Lectins / metabolism*
  • Monocytes / parasitology*
  • Monocytes / physiology*
  • Protein Kinase C / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Trichuris / physiology*

Substances

  • Antigens, CD
  • Cytokines
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor
  • Protein Kinase C