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.
| Authors: | Kooij G, Braster R, Koning JJ, Laan LC, van Vliet SJ, Los T, Eveleens AM, van der Pol SM, Förster-Waldl E, Boztug K, Belot A, Szilagyi K, van den Berg TK, van Buul JD, van Egmond M, de Vries HE, Cummings RD, Dijkstra CD, van Die I. |
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| Journal: | Acta Neuropathol Commun.;3:45. |
| Year: | 2015 |
| PubMed: | Find in PubMed |