Toxoplasma gondii infection in the peritoneal macrophages of rats treated with glucocorticoids

Abstract

It is well known that toxoplasmosis can be life threatening to immunocompromised individuals such as AIDS and organ transplantation patients. Glucocorticoids (GCs) are widely used in the clinic for the treatment of autoimmune diseases and organ transplantation resulting in acute toxoplasmosis in these patients. However, the interaction and mechanism between the development of acute toxoplasmosis and GC therapy are still unknown. The aims of this study were to investigate the infection of Toxoplasma gondii in the peritoneal macrophages of rats treated with glucocorticoids. Our results showed that the growth rate of T. gondii RH strain was significantly increased in the peritoneal macrophages of rats treated with glucocorticoids in vivo. For instance, 242 (±16) tachyzoites were found in 100 macrophages from the rats treated with methylprednisolone (MP), while only 16 (±4) tachyzoites were counted in the macrophages from the non-treated control rats 24 h after infection (P < 0.01). We also demonstrated that a significant inhibition of nitric oxide (NO) production was detected in the macrophages collected from the rats post-treated with GCs with 12.90 μM (±0.99 μM) of nitrite production from the rats treated with MP, while 30.85 μM (±1.62 μM) was found in the non-treated control rats 36 h after incubation (P < 0.01). Furthermore, glucocorticoids could significantly inhibit the expression of inducible nitric oxide synthase mRNA and its protein in the rat peritoneal macrophages. Our results strongly indicate that the decrease of NO in the rat peritoneal macrophages is closely linked to the cause of acute toxoplasmosis in the host. Additionally, there was a significant increase in the number of cysts produced by the naturally cyst forming, T. gondii Prugniaud strain with an average of 2,795 (±422) cysts of the parasite being detected in the brains of the rats treated with dexamethasone, while only 1,356 (±490) cysts were found in the non-treated control animals (P < 0.01). As rats and humans are both naturally resistant to T. gondii infection, these novel data could lead to a better understanding of the development of acute toxoplasmosis during glucocorticoid therapy in humans.

Investigation of infectivity of neonates and adults from different rat strains to Toxoplasma gondii Prugniaud shows both variation which correlates with iNOS and Arginase-1 activity and increased susceptibility of neonates to infection

“…BN and F344) conferred a higher degree of susceptibility to the cyst forming Toxoplasma strain than those with a higher ratio such as LEW, WST and SD. These results were further corroborated by another study in our laboratory (Wang et al, 2014). Wang and colleagues demonstrated that the treatment with glucocorticoids could significantly increase the cyst formation of T. gondii Prugniaud strain in F344 and data indicated that this treatment was linked to lower iNOS/Arg-1 ratios (Wang et al, 2014).…”

“…These results were further corroborated by another study in our laboratory (Wang et al, 2014). Wang and colleagues demonstrated that the treatment with glucocorticoids could significantly increase the cyst formation of T. gondii Prugniaud strain in F344 and data indicated that this treatment was linked to lower iNOS/Arg-1 ratios (Wang et al, 2014). This suggests that the resistance to Toxoplasma infection in different strains of rat is a significant genetic trait that is variable between strains which can be further modified by drug treatment.…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…Wang et al [741] showed that the growth rate of T. gondii RH strain tachyzoites was significantly increased in the peritoneal macrophages of rats treated with GCs in vivo compared with control cells (Table 28). They also demonstrated a significant inhibition of NO production in the macrophages collected from the rats receiving treatment with GCs compared with the control animals ( Table 29).…”

“…They also demonstrated a significant inhibition of NO production in the macrophages collected from the rats receiving treatment with GCs compared with the control animals ( Table 29). In addition, treatment with GCs inhibited the expression of iNOS mRNA in rat peritoneal macrophages [741] . [Nb.…”

“…GCs are widely used for the treatment of autoimmune diseases and after bone marrow transplantation, sometimes resulting in development of acute toxoplasmosis in these patients [741,749,750] . Approximately one-third of transplant recipients experienced neuropsychiatric and other complications including encephalopathy, stroke, seizures, loss of vision, cardiovascular events, and de novo lymphoproliferative disorders (lymphoma, glioma) [751][752][753][754] .…”