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.
Parasitol Res. 2014 Jan;113(1):351-8. doi: 10.1007/s00436-013-3661-3. Epub 2013 Nov 19.
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.
众所周知，弓形体病对免疫功能低下的个体（如艾滋病和器官移植患者）可能有生命威胁。糖皮质激素（GCs）广泛应用于临床治疗自身免疫性疾病和器官移植，导致这些患者发生急性弓形体病。然而，急性弓形体病的发展与 GC 治疗之间的相互作用和机制仍不清楚。本研究旨在探讨糖皮质激素治疗大鼠腹腔巨噬细胞感染弓形虫的情况。我们的研究结果表明，体内给予糖皮质激素治疗后，大鼠腹腔巨噬细胞中弓形虫 RH 株的生长速度明显加快。例如，用甲基强的松龙（MP）处理的大鼠腹腔巨噬细胞中发现 242（±16）个速殖子，而感染后 24 小时未经处理的对照组大鼠腹腔巨噬细胞中仅计数到 16（±4）个速殖子（P < 0.01）。我们还证明，GC 治疗后大鼠腹腔巨噬细胞中一氧化氮（NO）的产生受到显著抑制，用 MP 处理的大鼠产生 12.90 μM（±0.99 μM）的亚硝酸盐，而未经处理的对照组大鼠在孵育 36 小时后产生 30.85 μM（±1.62 μM）（P < 0.01）。此外，糖皮质激素可显著抑制大鼠腹腔巨噬细胞诱导型一氧化氮合酶 mRNA 及其蛋白的表达。我们的研究结果强烈表明，宿主中急性弓形体病的发生与大鼠腹腔巨噬细胞中 NO 的减少密切相关。此外，自然形成包囊的弓形虫 Prugniaud 株产生的包囊数量也显著增加，用地塞米松处理的大鼠脑中检测到平均 2795（±422）个寄生虫包囊，而未经处理的对照组动物中仅发现 1356（±490）个包囊（P < 0.01）。由于大鼠和人类对弓形虫感染均具有天然抗性，这些新数据可以帮助我们更好地理解人类在糖皮质激素治疗期间急性弓形体病的发展。
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