LPS‐induced TNFα production by macrophages is suppressed by a soluble product from the adult tapeworm, Hymenolepis diminuta

Abstract

Helminth parasites actively regulate their hosts’ immune response. Thus parasite‐derived molecules have the potential to be used to skew or suppress immune responses in humans as a way to treat immunopathology and disease. Seeking to exploit this we hypothesized that a product from H. diminuta would suppress macrophage activation. The human THP‐1 macrophage cell line was treated with LPS ± a high molecular weight fraction (HMWf: >50kDa) of H. diminuta. The HMWf reduced macrophage activation as assessed by TNFα and IL‐6 production in a time‐ and dose‐dependent manner. The ability of THP‐1 cells to phagocytose E. coli was unaffected by HMWf. RT‐PCR for the mannose receptor (up‐regulated on anti‐inflammatory macrophages) and Toll‐Like Receptor 4 (LPS receptor) mRNA revealed no differences between groups, indicating that the HMWf does not induce an alternatively activated macrophage or interfere with TLR4 expression. A HMWf from excretory/secretory (E/S) products from H. diminuta also reduced LPS‐induced TNFα production. The ability of the adult worm HMWf or the E/S products to block TNFα production by THP‐1 cells was insensitive to boiling or treatment with proteinase K. We conclude that a heat stable HMW product(s) from H. diminuta is a potent suppressor of macrophage activity, and that purification of this factor could serve as a template for drugs to block inflammatory disease. Funded by CCFC, CIHR & CAG.