1 University of Manchester, UK
DiscussionHelminth parasites are complex multicellular organisms capable of maintaining long lasting, chronic infections in human hosts. To ensure their survival and successful reproduction, helminth parasites have developed immunomodulatory mechanisms to modulate their host’s immune system to minimize the physical and immunological pathology to the host and prevent parasite expulsion. Many cells of the immune system are targets for parasite mediated immune modulation including T cells, macrophages and dendritic cells. In many inflammatory diseases, pro-inflammatory macrophages dominate causing significant pathology, therefore understanding how parasites modulate macrophage biology is important. To meet this need, bone marrow derived macrophages (BMDM) were used to (a) evaluate the ability of T. muris ES to down regulate pro-inflammatory macrophage responses; (b) explore the intracellular mechanisms underlying any immunomodulatory activity and (c) assess the potential of ES molecules to confer protection from inflammatory and autoimmune disorders. Pre-treatment of murine BMDMs with T. muris ES and its fractions significantly suppressed the expression of the pro-inflammatory mediators TNF, IL-27, CCL2, IL-6, IL-Iβ, and Nos2 upon LPS stimulation. T. muris ES also reduced the phosphorylation of p65 at serine 536, downregulated the expression of the histone acetyl transferase (HAT) p300 family, and upregulated the expression of histone deacetylases (HDACs). Thus, T. muris ES has the potential to limit the pathology associated with inflammatory and autoimmune diseases.