Laboratório de Genômica Funcional, Instituto Carlos Chagas, ICC-FIOCRUZ,Paraná, Brazil.
BMC Microbiol. 2012 Feb 9;12:22. doi: 10.1186/1471-2180-12-22.
The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.
The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells.
The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells.
利什曼原虫病的实验鼠模型已被广泛用于描述针对利什曼原虫的免疫反应。CBA 小鼠在感染 L. amazonensis 后会产生严重的病变，而 C57BL/6 则表现出小的慢性病变。采用转录组学方法结合生物网络分析，比较了 C57BL/6 和 CBA 巨噬细胞在体外感染 L. amazonensis 前后的基因表达谱。选择这两种品系是因为它们对寄生虫的易感性不同。
感染前后 C57BL/6 和 CBA 巨噬细胞表达的基因差异很大，无论是在绝对数量还是细胞功能方面。未感染的 C57BL/6 巨噬细胞表达的参与巨噬细胞失活途径的基因水平较低，而与宿主免疫炎症反应激活相关的基因，包括细胞凋亡和吞噬作用，表达水平升高。还观察到感染 L. amazonensis 的 C57BL/6 巨噬细胞中参与细胞凋亡过程的几个基因上调，这很可能与这些细胞控制寄生虫感染的能力有关。相比之下，感染后 CBA 巨噬细胞中参与脂质代谢的基因上调，这支持了 L. amazonensis 可能调节寄生泡以在宿主细胞中存活和繁殖的观点。
感染前后 C57BL/6 巨噬细胞的转录组谱参与了巨噬细胞激活途径，这可能有助于控制 L. amazonensis 感染，而 CBA 细胞的转录组谱则不然。
