Proliferation of Toxoplasma gondii in inflammatory macrophages in vivo is associated with diminished oxygen radical production in the host cell

Abstract

While reactive oxygen species (ROS) can kill Toxoplasma gondii in vitro the role these molecules play in vivo is not known. We used a flow cytometry-based assay to investigate the relationship between intracellular infection and ROS production during acute peritoneal toxoplasmosis in mice. A distinct population of ROS + inflammatory macrophages, detected by the oxidation of hydroethidine, was observed to increase progressively in frequency during the course of infection, and to be inversely correlated with the degree of cell parasitization. These data imply that either intracellular parasites inhibit ROS synthesis or, alternatively, ROS-producing cells contain antiToxoplasma activity. The latter interpretation was supported by the finding that uninfected ROSproducing inflammatory macrophages were resistant to infection in vivo. However, in the same animals, ROS-producing macrophages that had previously been parasitized could readily be infected with additional parasites, suggesting that the difference in ROS production between highly infected and less infected cells was not due to ROS-associated killing of parasites within these cells. In addition, macrophages infected with T. gondii in vitro and then briefly transferred to acutely infected mice upregulated ROS production in a manner that was again inversely correlated with the degree of intracellular parasitization. Taken together, these findings suggest that both ROS-associated anti-Toxoplasma activity and parasite-driven inhibition of ROS production underlie the observed pattern of ROS production. ROS function and parasite evasion of this function may contribute significantly to the balance between host defense and disease progression during acute infection.

Oral immunostimulation of the oyster Ostrea edulis: Impacts on the parasite Bonamia ostreae

“…The role of ROS as an effective defensive mechanism against pathogens has been recently questioned [68]. As occurs in other intracellular parasites of the genus Toxoplasma and Leishmania [69,70], B. ostreae can reduce the oxidative burst for its own benefit [32]. Moreover, it was described that ROS can increase parasite burden and the use of antioxidants was postulated as a therapeutic strategy in certain virus infections [68].…”

Infection with the protozoan parasite Bonamia ostreae modifies in vitro haemocyte activities of flat oyster Ostrea edulis

“…As no cell mortality was detected, parasites may have a direct impact on haemocyte ROS production. The inhibition of oxygen radical production facilitates intracellular survival of protozoan parasites including Trypanosoma sp [53], Toxoplasma sp [54,55] and Leishmania sp [56].…”

Inhibition of Toxoplasma gondii and Plasmodium falciparum Infections in Vitro by NSC3852, a Redox Active Antiproliferative and Tumor Cell Differentiation Agent

“…obs.). Thus, despite the ability of human fibroblasts to generate ROS and NO via NADPH oxidase and NOS, respectively (Shen et al, 2006;Sterin-Borda et al, 2007), and the known sensitivity of T. gondii to these free radicals (Stafford et al, 2002;Shrestha et al, 2006), NSC3852 works differently against T. gondii.…”

“…Immunologic defense against acute toxoplasmosis requires a robust CD8ϩ T-cell response and interferon-gamma-mediated activation of macrophages (Beaman et al, 1994;Abou-Bacar et al, 2004;Buzoni-Gatel and Werts, 2006;Miller et al, 2006). Activated macrophages exert anti-T. gondii activity by producing reactive oxygen species (ROS) and nitric oxide (NO) (Stafford et al, 2002;Shrestha et al, 2006). Redox active enzymes expressed in T. gondii tachyzoites and P. falciparum have been scrutinized, and the antioxidant enzymes that are likely to maintain parasite survival during intracellular growth, as well as during their extracellular transit prior to infection of new host cells, have been identified as potential new targets for drug development (Ding et al, 2004;Pino et al, 2007).…”