Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama City, Panama, Republic of Panama.
Departamento de Biotecnología, Facultad de Ciencias de la Salud, Universidad Latina de Panamá, Panama City, Panama, Republic of Panama.
PLoS Negl Trop Dis. 2021 Feb 22;15(2):e0009225. doi: 10.1371/journal.pntd.0009225. eCollection 2021 Feb.
Leishmania parasites can trigger different host immune responses that result in varying levels of disease severity. The C57BL/6 and BALB/c mouse strains are among the host models commonly used for characterizing the immunopathogenesis of Leishmania species and the possible antileishmanial effect of novel drug candidates. C57BL/6 mice tend to be resistant to Leishmania infections, whereas BALB/c mice display a susceptible phenotype. Studying species-specific interactions between Leishmania parasites and different host systems is a key step to characterize and validate these models for in vivo studies. Here, we use RNA-Seq and differential expression analysis to characterize the transcriptomic profiles of C57BL/6 and BALB/c peritoneal-derived macrophages in response to Leishmania panamensis infection. We observed differences between BALB/c and C57BL/6 macrophages regarding pathways associated with lysosomal degradation, arginine metabolism and the regulation of cell cycle. We also observed differences in the expression of chemokine and cytokine genes associated with regulation of immune responses. In conclusion, infection with L. panamensis induced an inflammatory gene expression pattern in C57BL/6 macrophages that is more consistently associated with a classic macrophage M1 activation, whereas in BALB/c macrophages a gene expression pattern consistent with an intermediate inflammatory response was observed.
利什曼原虫寄生虫可引发不同的宿主免疫反应，从而导致疾病严重程度的不同。C57BL/6 和 BALB/c 两种小鼠品系是用于描述利什曼原虫物种的免疫发病机制和新型候选药物可能的抗利什曼作用的常用宿主模型之一。C57BL/6 小鼠通常对利什曼原虫感染具有抵抗力，而 BALB/c 小鼠则表现出易感表型。研究利什曼原虫寄生虫与不同宿主系统之间的种间相互作用，是对这些模型进行体内研究进行特征描述和验证的关键步骤。在这里，我们使用 RNA-Seq 和差异表达分析来描述 C57BL/6 和 BALB/c 腹膜衍生巨噬细胞对巴拿马利什曼原虫感染的转录组谱。我们观察到 BALB/c 和 C57BL/6 巨噬细胞在与溶酶体降解、精氨酸代谢和细胞周期调控相关的途径上存在差异。我们还观察到与免疫反应调控相关的趋化因子和细胞因子基因表达的差异。总之，L. panamensis 的感染诱导了 C57BL/6 巨噬细胞中炎症基因表达模式，该模式与经典的巨噬细胞 M1 激活更为一致，而在 BALB/c 巨噬细胞中则观察到与中间炎症反应一致的基因表达模式。
