Setaria digitata secreted filarial lipids modulate IL-12 signaling through JAK-STAT pathway leading to the development of Th1 response

Filariasis is a debilitating parasitic disease in many tropical countries. Despite the highly evolved immune system, the filarial parasites successfully evade host immunity to persist for a sustained period of time. Earlier studies have shown that the filarial parasites achieve this long-term survival through release of inummosuppressive materials in the host. In this study, we show that the secreted filarial lipids (SFL) isolated from Setaria digitata suppress Th1 immune response. While immunization with myelin antigen induces Th1 response in mice, in vitro treatment with SFL resulted in a dose-dependent decrease in myelin antigen-induced proliferation and secretion of IL-12 and IFN gamma. The SFL also inhibited IL-12-induced T cell proliferation and Th1 differentiation in vitro. The inhibition of T cell responses by SFL associates with the blockade of IL-12-induced activation of JAK-STAT signaling pathway in T cells. These findings suggest that the SFL modulates Th1 immune response by blocking IL-12 signaling in T cells and thus play a role in host immune evasion of filarial parasites. (c) 2006 Elsevier Inc. All rights reserved.