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

Gijs Kooij,Lisa C Laan,Helga E De Vries,Richard D Cummings,Elisabeth Förster-Waldl,Anne Marieke Eveleens,Rens Braster,Marjolein Van Egmond,Kaan Boztug,Alexandre Belot,Timo K Van Den Berg,Jaap D Van Buul,Sandra J Van Vliet,Christine D Dijkstra,Irma Van Die,Katka Szilagyi,Tamara Los,Susanne M A Van Der Pol,Jasper J Koning

doi:10.1186/s40478-015-0223-1

Abstract

IntroductionThe 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.ResultsHere 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.ConclusionThis study provides comprehensive mechanistic insight into helminth-induced immunomodulation, which can be therapeutically exploited to combat various auto-immune disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0223-1) contains supplementary material, which is available to authorized users.

Highlights

The inverse correlation between prevalence of auto-immune disorders like the chronic neuroinflammatory disease multiple sclerosis (MS) and the occurrence of helminth infections, suggests that the helminth-trained immune system is protective against auto-immunity
We have recently reported that T. suis soluble products (TsSP) suppresses pro-inflammatory responses in monocyte-derived macrophages [10], which are key players in MS pathogenesis, as these cells are responsible for axonal loss and neurodegeneration [11]
TsSP induce a shift from classical to non-classical human monocytes To identify the pathways by which T. suis soluble products (TsSP) affect the innate immune system, we first investigated whether TsSP causes changes in the phenotype of human blood monocytes

Summary

Introduction

The inverse correlation between prevalence of auto-immune disorders like the chronic neuroinflammatory disease multiple sclerosis (MS) and the occurrence of helminth (worm) infections, suggests that the helminth-trained immune system is protective against auto-immunity. We have recently reported that TsSP suppresses pro-inflammatory responses in monocyte-derived macrophages [10], which are key players in MS pathogenesis, as these cells are responsible for axonal loss and neurodegeneration [11]. These findings suggest that the observed beneficial effects of TsSP in MS patients may be explained by a direct effect on innate immunity, and this hypothesis will be addressed in the current study. Research is needed to identify molecules and mechanisms that can skew these inflammatory monocytes into antiinflammatory [16] and wound healing [20] patrolling cells that exhibit reduced transendothelial migration capacity, and thereby provide novel ways to combat disease progression

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Conclusion