Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
Int J Parasitol. 2010 Jun;40(7):797-805. doi: 10.1016/j.ijpara.2009.12.003. Epub 2010 Jan 7.
Neospora caninum, the causative agent of neosporosis, is an obligate intracellular parasite considered to be a major cause of abortion in cattle throughout the world. Most studies concerning N. caninum have focused on life cycle, seroepidemiology, pathology and vaccination, while data on host-parasite interaction, such as host cell migration, mechanisms of evasion and dissemination of this parasite during the early phase of infection are still poorly understood. Here we show the ability of excreted/secreted antigens from N. caninum (NcESAs) to attract monocytic cells to the site of primary infection in both in vitro and in vivo assays. Molecules from the family of cyclophilins present on the NcESAs were shown to work as chemokine-like proteins and NcESA-induced chemoattraction involved G(i) protein signaling and participation of CC-chemokine receptor 5 (CCR5). Additionally, we demonstrate the ability of NcESAs to enhance the expression of CCR5 on monocytic cells and this increase occurred in parallel with the chemotactic activity of NcESAs by increasing cell migration. These results suggest that during the first days of infection, N. caninum produces molecules capable of inducing monocytic cell migration to the sites of infection, which will consequently enhance initial parasite invasion and proliferation. Altogether, these results help to clarify some key features involved in the process of cell migration and may reveal virulence factors and therapeutic targets to control neosporosis.
刚地弓形虫是刚地弓形虫病的病原体，是一种专性细胞内寄生虫，被认为是全世界牛流产的主要原因。大多数关于刚地弓形虫的研究都集中在生命周期、血清流行病学、病理学和疫苗接种上，而关于宿主-寄生虫相互作用的数据，如宿主细胞迁移、这种寄生虫在感染早期逃避和传播的机制，仍然知之甚少。在这里，我们展示了刚地弓形虫（NcESAs）分泌/分泌的抗原吸引单核细胞迁移到原发性感染部位的能力，无论是在体外还是体内实验中。NcESAs 上存在的亲环素家族的分子被证明是类趋化因子蛋白，NcESA 诱导的趋化作用涉及 G(i)蛋白信号和 CC 趋化因子受体 5（CCR5）的参与。此外，我们证明了 NcESAs 能够增强单核细胞上 CCR5 的表达，并且这种增加与 NcESAs 的趋化活性平行发生，增加了细胞迁移。这些结果表明，在感染的最初几天，刚地弓形虫产生的分子能够诱导单核细胞迁移到感染部位，从而增强寄生虫的初始入侵和增殖。总的来说，这些结果有助于阐明细胞迁移过程中涉及的一些关键特征，并可能揭示控制弓形虫病的毒力因子和治疗靶点。
