Suppressed production of pro-inflammatory cytokines by LPS-activated macrophages after treatment with Toxoplasma gondii lysate

Abstract

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of pro- and anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LIPS). Treatment of THP-1 cells with LIPS induced production of IL-12, TNF-alpha, IL-8 and IL-10 Co-treatment of THP-1 cells with T gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-alpha expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like reoeptor (TLR)-2 and TLR4 antibodies. T gondii lysate triggered nuclear factor (NF)-kappa B-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T gondii lysate treatment might occur via TLR2-mediated NF-kappa B activation.