title: 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.
authors.affiliation: Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences and Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510275, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jiang-Mei
authors.initials: JM
authors.lastname: Gao
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Yi
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Geng
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Gao
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Shen
authors.forename: Fang-Li
authors.initials: FL
authors.lastname: Lu
authors.forename: Yan-Zi
authors.initials: YZ
authors.lastname: Wen
authors.forename: Geoff
authors.initials: G
authors.lastname: Hide
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000469:parasitology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014122:Toxoplasma / Q000254:growth & development*; D014124:Toxoplasmosis, Animal / Q000276:immunology
chemical_list: D005938:Glucocorticoids; D009569:Nitric Oxide; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006854:Hydrocortisone; D008775:Methylprednisolone