Suppression of NF‐κB Activation by Infection withToxoplasma gondii

Abstract

The interaction of host cells with microbial products or their invasion by pathogens frequently results in activation of the NF-kappaB family of transcription factors. The studies presented here reveal that in vivo, infection with Toxoplasma gondii results in the activation of NF-kappaB. To determine whether host cells could activate NF-kappaB in response to invasion by T. gondii, Western blots, immunofluorescence, and electrophoretic mobility shift assays were used to assess the response of host cells to infection. In these studies, infection of macrophages or fibroblasts with T. gondii did not result in the activation of NF-kappaB. In addition, the ability of lipopolysaccharide to activate NF-kappaB was impaired in cultures of macrophages infected with T. gondii. Together, these data demonstrate that invasion of cells by T. gondii does not lead to the activation of NF-kappaB and suggest that the parasite may actively interfere with the pathways that lead to NF-kappaB activation.

Toxoplasma gondii Virulence Factor ROP18 Inhibits the Host NF-κB Pathway by Promoting p65 Degradation

“…However, despite the initiation of NF-B signaling, infection with T. gondii did not lead to the activation of NF-B but to its termination. The reason for disabling NF-B is associated with blocking of p65 translocation to the nucleus (10,12,13). Other studies have demonstrated that T. gondii activates NF-B, which up-regulates the expression of anti-apoptotic genes to facilitate the replication of the pathogen (15)(16)(17).…”

Host cell manipulation by the human pathogen Toxoplasma gondii

“…This observation demonstrated the importance of NF-κB p65 component as a key factor in the protection of the infected fibroblast against apoptosis [99]. It should be noted, however, that movement of NF-κB to the nucleus is not observed in all types of infected cells including macrophages, which do not exhibit NF-κB translocation early after invasion [105][106][107]. This may be due to inherent differences between cell types or a result of examining translocation at different time points post-invasion.…”

Roles of Glycosylphosphatidylinositols of Toxoplasma gondii

“…Experiments performed with protein kinase inhibitors suggest that the synthesis of TNF␣, induced by soluble antigen of T. gondii, is protein kinase C-dependent, whereas the kinase does not appear to play a dominant role in soluble antigeninduced IL-12 and IL-10 responses, arguing that distinct parasite signals are involved in monokine induction (14). In vivo infection of mice with virulent or avirulent strains of T. gondii leads to activation of NF-B in peritoneal cells (37). In contrast, Butcher and Denkers (19) have no evidence for NF-B p65 translocation in peritoneal cells of mice infected in vivo with a virulent strain of T. gondii.…”