Ottow, M. K.2; Klaver, E. J.2; van der Pouw Kraan, T. C. T. M.2; Heijnen, P. D.2; Laan, L. C.2; Kringel, Helene4; Vogel, D. Y. S.2; Dijkstra, C. D.2; Kooij, G.2; van Die, I.2
1 Parasitology and Aquatic Diseases, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet2 VU University Medical Center3 Section of Parasitology, Health and Development, Department of Veterinary Disease Biology, Faculty of Life Sciences, Københavns Universitet4 Section of Parasitology, Health and Development, Department of Veterinary Disease Biology, Faculty of Life Sciences, Københavns Universitet
Recent clinical trials in patients with inflammatory diseases like multiple sclerosis (MS) or inflammatory bowel disease (IBD) have shown the beneficial effects of probiotic helminth administration, although the underlying mechanism of action remains largely unknown. Potential cellular targets may include innate immune cells that propagate inflammation in these diseases, like pro-inflammatory macrophages. We here investigated the effects of the helminth Trichuris suis soluble products (SPs) on the phenotype and function of human inflammatory (granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated) macrophages. Interestingly, we here show that T. suis SPs potently skew inflammatory macrophages into a more anti-inflammatory state in a Toll-like receptor 4 (TLR4)-dependent manner, and less effects are seen when stimulating macrophages with TLR2 or -3 ligands. Gene microarray analysis of GM-CSF-differentiated macrophages further revealed that many TLR4-induced inflammatory mediators, including interleukin (IL)-12B, CCL1 and CXCL9, are downregulated by T. suis SPs. In particular, we observed a strong reduction in the expression and function of P2RX7, a purinergic receptor involved in macrophage inflammation, leading to reduced IL-1β secretion. In conclusion, we show that T. suis SPs suppress a broad range of inflammatory pathways in GM-CSF-differentiated macrophages in a TLR4-dependent manner, thereby providing enhanced mechanistic insight into the therapeutic potential of this helminth for patients with inflammatory diseases.Genes and Immunity advance online publication, 10 July 2014; doi:10.1038/gene.2014.38.
Genes and Immunity, 2014, Vol 15, Issue 7, p. 477-486