Ahmed Fahmy Mennat-Elrahman, Abdel-Aal Amany Ahmed, Shalaby Maisa Ahmed, Issa Ragaa, Badawi Manal, Fouly Marwa A
Department of Medical Parasitology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt.
Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Parasit Dis. 2024 Mar;48(1):33-45. doi: 10.1007/s12639-023-01635-1. Epub 2023 Dec 5.
Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly ( < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.
眼部弓形虫病可能是全球感染性后葡萄膜炎最常见的病因。CXCL10趋化因子在慢性感染期间维持T细胞反应及控制眼部感染方面发挥着重要作用。能够调节趋化因子活性的药物可能对该寄生虫有效。在本研究中，首次在患有眼部弓形虫病的糖尿病小鼠模型中研究了CXCLl0在视网膜局部的表达情况。此外，还比较了萘醌类和喹诺酮类药物与螺旋霉素(SP)在治疗感染及调节趋化因子表达方面的效果。我们的研究结果显示，氯喹(CQ)在减轻脑囊肿负担方面效果最佳(84.36%)，显著改善了视网膜组织病理学变化、细胞浸润及血管炎(P<0.005)，并平衡了由感染引起的强烈的CXCL10表达。经丁萘醌治疗的小鼠脑囊肿减少比例显著(76.25%)，组织病理学有中度改善，CXCL10表达呈轻度至中度。而SP对眼部寄生虫的疗效最差，仅使组织病理学变化有轻度改善，视网膜趋化因子表达下调，脑内寄生虫负担减轻率最低(57%)。总之，对病原体的最佳控制可能需要趋化因子适度表达的平衡免疫反应。因此，针对视网膜CXCL10的调节可能最终有利于眼部弓形虫病的治疗，并且其有可能作为感染期间预测局部免疫反应的标志物。
