期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 3, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s40478-015-0223-1
关键词
Auto-immunity; Multiple sclerosis; Innate immunity; Trichuris suis; Monocytes; Mannose receptor; Protein kinase C; PKC delta
资金
- National Multiple Sclerosis Society [PP1686]
- Dutch MS Research Foundation [MS 11-771]
- National Institute of Health [AI101982]
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.
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