INMIVET, Department of Animal Health, Faculty of Veterinary Science, Complutense University of Madrid, 28040 Madrid, Spain.
Centro Nacional de Secuenciación Genómica-CNSG, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellín 050010, Colombia.
Int J Mol Sci. 2022 Jan 27;23(3):1466. doi: 10.3390/ijms23031466.
Zoonotic visceral leishmaniosis caused by is an endemic disease in the Mediterranean Basin affecting mainly humans and dogs, the main reservoir. The leishmaniosis outbreak declared in the Community of Madrid (Spain) led to a significant increase in human disease incidence without enhancing canine leishmaniosis prevalence, suggesting a better adaptation of the outbreak's isolates by other host species. One of the isolates obtained in the focus, IPER/ES/2012/BOS1FL1 (BOS1FL1), has previously demonstrated a different phenotype than the reference strain MCAN/ES/1996/BCN150 (BCN150), characterized by a lower infectivity when interacting with canine macrophages. Nevertheless, not enough changes in the cell defensive response were found to support their different behavior. Thus, we decided to investigate the molecular mechanisms involved in the interaction of both parasites with DH82 canine macrophages by studying their transcriptomic profiles developed after infection using RNA sequencing. The results showed a common regulation induced by both parasites in the phosphoinositide-3-kinase-protein kinase B/Akt and NOD-like receptor signaling pathways. However, other pathways, such as phagocytosis and signal transduction, including tumor necrosis factor, mitogen-activated kinases and nuclear factor-κB, were only regulated after infection with BOS1FL1. These differences could contribute to the reduced infection ability of the outbreak isolates in canine cells. Our results open a new avenue to investigate the true role of adaptation of isolates in their interaction with their different hosts.
由 引起的动物源性内脏利什曼病是地中海盆地的地方性疾病，主要影响人类和狗，狗是主要的宿主。在马德里社区（西班牙）宣布的利什曼病爆发导致人类疾病发病率显著增加，而犬利什曼病的流行率没有增加，这表明爆发的分离株在其他宿主物种中更好地适应了环境。在该焦点中获得的分离株之一，IPER/ES/2012/BOS1FL1（BOS1FL1），以前表现出与参考株 MCAN/ES/1996/BCN150（BCN150）不同的表型，其与犬巨噬细胞相互作用时的感染力较低。然而，在细胞防御反应中没有发现足够的变化来支持它们的不同行为。因此，我们决定通过研究感染后使用 RNA 测序开发的转录组图谱，研究这两种寄生虫与 DH82 犬巨噬细胞相互作用所涉及的分子机制。结果表明，两种寄生虫都能共同诱导磷酸肌醇-3-激酶-蛋白激酶 B/Akt 和 NOD 样受体信号通路的调控。然而，其他途径，如吞噬作用和信号转导，包括肿瘤坏死因子、有丝分裂原激活的蛋白激酶和核因子-κB，仅在感染 BOS1FL1 后才受到调控。这些差异可能导致爆发分离株在犬细胞中的感染能力降低。我们的研究结果为研究 分离株在与不同宿主相互作用中的适应性的真正作用开辟了新途径。
