Regulation of inflammatory diseases by cestode antigens: multiple receptors and a possible common pathway (P3128)

Abstract

Abstract Helminth parasites bias the immune response toward Th2 and/or to a regulatory environment associated with high levels of IL-4, IL-13, IL-5 and IL-10. In addition, helminth infections impair immunity against other unrelated infections. Thus, helminths can modulate the immune response in their host, and they have multiple ways to escape or modulate the immune system. One of their potential evasion strategies involves modulating the early response of macrophages and dendritic cells (DCs). These modulatory activities have been exploited to interferer development of pro-inflammatory-mediated diseases such as arthritis (AR), type 1 diabetes (T1D), experimental autoimmune encephalomyelitis (EAE) and colitis. Here we show that Taenia crassiceps, a cestode, is able to ameliorate the severity of EAE, T1D and colitis, but not AR, mainly by down-regulating IL-12, TNF-a, IL-15, IL-17, IL-1b and NO production. However, as most of the effects of helminth infections in these kinds of diseases, the mechanisms involved remain mainly unknown. Using T. crassiceps antigens we reproduced the effects of the infection. Such antigens are rich in glycoproteins that appear to be binding by multiple receptors, including MGL, MR, and TLR2, and interfered with the inflammatory-induced NFκB p65 and p38 MAPK pathways. Interestingly, blockade of just one intracellular signaling pathway was enough to avoid the effect of T. crassiceps antigens on modulating DCs and programing Th2 responses.