Iqbal Jamshaid, Al-Awadhi Mohammad Ahmed, Raghupathy Raj Gopal
Department of Microbiology, Faculty of Medicine, Kuwait University, PO Box: 24923, Safat 13110, Kuwait.
Department of Microbiology, Faculty of Medicine, Kuwait University, PO Box: 24923, Safat 13110, Kuwait.
Exp Parasitol. 2016 Mar;162:57-63. doi: 10.1016/j.exppara.2016.01.003. Epub 2016 Jan 8.
Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinochoroiditis in cases of congenital infection leading to blindness. The importance of host genetics in determining disease severity in ocular toxoplasmosis has been shown in different inbred mouse strains using low-virulence toxoplasma strain. In this study, we studied intraocular immune response and tissue alterations in the genetically resistant BALB/c and susceptible MF1 mice infected with a virulent type I RH Toxoplasma gondii strain by intravitreal route. We observed a significant up-regulation of IFN-γ and TNF-α to >2200 pg/ml and >300 pg/ml respectively in the blood of both BALB/c and MF1mice during the early stages of post intraocular infection (p < 0.01) but the levels dropped sharply to normal during the late stages of the infection on day 26. The cytokine levels detected were higher in the MF1 mice compared with the BALB/c mice and a relatively higher levels were observed in the aqueous humour (AqH) than in the blood of both group of mice. The TGF-β1 level in the blood and AqH of BALB/c mice remained low throughout the infection period compared with MF1 mice which showed gradual increase to 50 pg/ml in the blood and AqH during the early stages of infection which then further increased 2-fold-132 pg/ml on day 11 (p < 0.01) and remained high till the last day of observation on day 26 except that the TGF-β1 level in AqH dropped sharply to normal level. In summary, our results support that TGF-β1 may down-regulate the effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis. We document that a mild Th1 pro-inflammatory response in the BALB/c mice with high IFN-γ and TNF-α and, low TGF-β1 levels during the early stages of infection may have contributed to an effective cellular immune response leading to lower morbidity, mortality and less ocular tissue damage. However in the MF1 mice, a significantly high TGF-β1 level in the blood as well as in the AqH during the acute intra-ocular toxoplasma infection may have adversely interfered with an effective cellular immune response leading to an increased mortality and extensive ocular tissue damage with parasite tachyzoites observed in the pigment epithelium layers.
弓形虫病在健康成年人中通常是自限性的，但在先天性感染的情况下可能会导致弓形虫性视网膜脉络膜炎，进而导致失明。利用低毒力弓形虫菌株，在不同的近交系小鼠品系中已显示宿主遗传学在决定眼部弓形虫病的疾病严重程度方面的重要性。在本研究中，我们通过玻璃体内途径，研究了感染强毒株I型RH刚地弓形虫的基因抗性BALB/c小鼠和易感MF1小鼠的眼内免疫反应和组织改变。我们观察到，在眼内感染后的早期阶段，BALB/c小鼠和MF1小鼠血液中的IFN-γ和TNF-α均显著上调，分别>2200 pg/ml和>300 pg/ml（p<0.01），但在感染后期的第26天，其水平急剧下降至正常。检测到的细胞因子水平在MF1小鼠中高于BALB/c小鼠，并且在两组小鼠的房水中观察到的水平相对高于血液中的水平。与MF1小鼠相比，BALB/c小鼠血液和房水中的TGF-β1水平在整个感染期都保持较低，MF1小鼠在感染早期血液和房水中的TGF-β1水平逐渐升高至50 pg/ml，然后在第11天进一步升高2倍至132 pg/ml（p<0.01），并一直保持高水平直至观察的最后一天即第26天，只是房水中的TGF-β1水平急剧下降至正常水平。总之，我们的结果支持TGF-β1可能在急性弓形虫病期间下调抗弓形虫细胞免疫的效应功能。我们记录到，在感染早期，BALB/c小鼠中具有高IFN-γ和TNF-α以及低TGF-β1水平的轻度Th1促炎反应可能有助于产生有效的细胞免疫反应，从而导致较低的发病率、死亡率和较少的眼组织损伤。然而，在MF1小鼠中，急性眼内弓形虫感染期间血液和房水中显著高的TGF-β1水平可能对有效的细胞免疫反应产生了不利干扰，导致死亡率增加和广泛的眼组织损伤，在色素上皮层中观察到寄生虫速殖子。
