Honoré S, Garin Y J, Sulahian A, Gangneux J P, Derouin F
Laboratoire de Parasitologie-Mycologie, Faculté de Médecine Lariboisière-Saint-Louis, Université Paris 7, France.
FEMS Immunol Med Microbiol. 1998 Jul;21(3):231-9. doi: 10.1111/j.1574-695X.1998.tb01170.x.
We investigated the respective roles of the host and parasite strain in a murine model of visceral leishmaniasis. Balb/c and C57Bl/6 mice were selected for their respective 'non cure' and 'cure' haplotypes vis-a-vis Leishmania major. Mice were infected with 10(7) stationary-phase promastigotes of four strains of Leishmania infantum with different infection profiles in mice: visceralization or regulation, as established by Sulahian et al. (Sulahian et al. (1998) FEMS Immunol. Med. Microbiol. 17, 131-138). The infection was monitored by measuring parasite load in the liver and spleen on days 9, 22, 44 and 87 post-infection, using a sensitive microtitration technique. Similar profiles (visceralizing or regulating) were observed in the two mouse strains, suggesting a predominant role of the Leishmania strain in the visceralization process. The host response was assessed by analyzing the granulomatous response in the liver and by quantifying specific IgG, IgG1 and IgG2a as a marker of the Th1/Th2 immune response. A granulomatous response was observed in both strains of mice but was more pronounced with visceralizing strains of L. infantum and in C57Bl/6 mice compared to Balb/c mice. The kinetics of anti-Leishmania IgG antibody production was similar in all the groups, but the distribution of IgG1 and IgG2a isotypes was different between the two mouse strains: Balb/c mice had a predominantly Th2-like response whereas C57Bl/6 had a mixed Th1/Th2-like response. This study demonstrates the determining role of both the parasite and mouse strain in the outcome of L. infantum infection. The Th1/Th2 concept does not seem to explain susceptibility and resistance to infection in our model of visceral L. infantum infection, contrary to the L. major model.
我们在内脏利什曼病的小鼠模型中研究了宿主和寄生虫菌株各自的作用。相对于硕大利什曼原虫，选择Balb/c和C57Bl/6小鼠分别因其各自的“不治愈”和“治愈”单倍型。小鼠用四株婴儿利什曼原虫的10⁷个静止期前鞭毛体感染，这些菌株在小鼠中具有不同的感染特征：内脏化或调节，这是由Sulahian等人确定的（Sulahian等人，(1998) FEMS Immunol. Med. Microbiol. 17, 131 - 138）。在感染后第9、22、44和87天，使用灵敏的微量滴定技术通过测量肝脏和脾脏中的寄生虫负荷来监测感染情况。在两种小鼠品系中观察到相似的特征（内脏化或调节），表明利什曼原虫菌株在内脏化过程中起主要作用。通过分析肝脏中的肉芽肿反应并定量特异性IgG、IgG1和IgG2a作为Th1/Th2免疫反应的标志物来评估宿主反应。在两种小鼠品系中均观察到肉芽肿反应，但与Balb/c小鼠相比，婴儿利什曼原虫内脏化菌株和C57Bl/6小鼠中的反应更明显。所有组中抗利什曼原虫IgG抗体产生的动力学相似，但两种小鼠品系之间IgG1和IgG2a同种型的分布不同：Balb/c小鼠主要有Th2样反应，而C57Bl/6有混合的Th1/Th2样反应。本研究证明了寄生虫和小鼠品系在婴儿利什曼原虫感染结果中的决定性作用。与硕大利什曼原虫模型相反，Th1/Th2概念似乎无法解释我们的内脏婴儿利什曼原虫感染模型中的易感性和抗性。
