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

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.

• Authors: Gijs Kooij, Rens Braster, Jasper J Koning, Lisa C Laan, Sandra J van Vliet, Tamara Los, Anne Marieke Eveleens, Susanne M A van der Pol, Elisabeth Förster-Waldl, Kaan Boztug, Alexandre Belot, Katka Szilagyi, Timo K van den Berg, Jaap D van Buul, Marjolein van Egmond, Helga E de Vries, Richard D Cummings, Christine D Dijkstra, Irma van Die
• Journal: Acta neuropathologica communications (Acta Neuropathol Commun) Vol. 3 Pg. 45 (Jul 25 2015) ISSN: 2051-5960 [Electronic] England
• PMID: 26205402 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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