Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Department of Structural Biology, VIB, Brussels, Belgium.
Parasite Immunol. 2014 May;36(5):187-98. doi: 10.1111/pim.12099.
Trypanosoma congolense is one of the main species responsible for Animal African Trypanosomosis (AAT). As preventive vaccination strategies for AAT have been unsuccessful so far, investigating the mechanisms underlying vaccine failure has to be prioritized. In T. brucei and T. vivax infections, recent studies revealed a rapid onset of destruction of the host B-cell compartment, resulting in the loss of memory recall capacity. To assess such effect in experimental T. congolense trypanosomosis, we performed infections with both the cloned Tc13 parasite, which is considered as a standard model system for T. congolense rodent infections and the noncloned TRT55 field isolate. These infections differ in their virulence level in the C57BL/6 mouse model for trypanosomosis. We show that early on, an irreversible depletion of all developmental B cells stages occur. Subsequently, in the spleen, a detrimental decrease in immature B cells is followed by a significant and permanent depletion of Marginal zone B cells and Follicular B cells. The severity of these events later on in infection correlated with the virulence level of the parasite stock. In line with this, it was observed that later-stage infection-induced IgGs were largely nonspecific, in particular in the more virulent TRT55 infection model.
冈比亚锥虫是导致动物非洲锥虫病(AAT)的主要物种之一。由于迄今为止预防接种策略对 AAT 都不成功,因此必须优先研究疫苗失败的机制。在布氏锥虫和恰加斯锥虫感染中,最近的研究揭示了宿主 B 细胞区室迅速破坏的现象,导致记忆召回能力丧失。为了在实验性刚果锥虫锥虫病中评估这种效应,我们进行了两种感染实验,一种是用被认为是刚果锥虫啮齿动物感染标准模型系统的克隆 Tc13 寄生虫进行感染,另一种是用非克隆 TRT55 野外分离株进行感染。这些感染在 C57BL/6 小鼠模型中的毒力水平不同。我们表明,早期所有发育中的 B 细胞阶段都会发生不可逆转的耗竭。随后,在脾脏中,不成熟 B 细胞的有害减少之后,边缘区 B 细胞和滤泡 B 细胞显著且永久耗竭。这些事件在感染后期的严重程度与寄生虫株的毒力水平相关。与此一致的是,观察到后期感染诱导的 IgG 大部分是非特异性的,特别是在毒力更强的 TRT55 感染模型中。