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

G. Kooij, R. Braster, J.J. Koning, L.C. Laan, S.J. van Vliet, T. Los, A.M. Eveleens, S.M.A. van der Pol, E. Forster-Waldl, K. Boztug, A. Belot, K. Szilagyi, T.K. van den Berg, J.D. van Buul, M. van Egmond, H.E. de Vries, R.D. Cummings, C.D. Dijkstra, I. van Die, Elisabeth Förster-Waldl

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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 PKC delta. Conclusion: This study provides comprehensive mechanistic insight into helminth-induced immunomodulation, which can be therapeutically exploited to combat various auto-immune disorders
Original languageUndefined/Unknown
Article number45
Pages (from-to)45
JournalActa Neuropathologica Communinications
Volume3
Issue number1
DOIs
Publication statusPublished - 2015

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