Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1466
• Main Authors: Mas, Alicia, Martínez-Rodrigo, Abel, Carrión, Javier, Orden, José Antonio, Alzate, Juan F, Domínguez-Bernal, Gustavo, Horcajo, Pilar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.01.2022; MDPI
• Subjects: Adaptation; AKT protein; Animals; canine macrophage; Cell Line; Defensive behavior; DH82 cells; Dogs - genetics; Dogs - parasitology; Gene expression; Gene Expression Regulation; Gene Ontology; Genomes; Infections; Infectivity; Kinases; Leishmania infantum; Leishmania infantum - growth & development; Leishmania infantum - pathogenicity; Leishmaniasis; Leishmaniasis, Visceral - genetics; Leishmaniasis, Visceral - parasitology; Leishmaniasis, Visceral - veterinary; Life Cycle Stages - physiology; Macrophages; Macrophages - metabolism; Macrophages - parasitology; Molecular modelling; NLR Proteins - metabolism; Outbreaks; Parasites; Parasitic diseases; Phagocytosis; Phenotypes; Phosphatidylinositol 3-Kinases - metabolism; Promastigotes; Proto-Oncogene Proteins c-akt - metabolism; Reproducibility; RNA-seq; Signal Transduction; Transcriptome - genetics; Transcriptomics; Virulence; Zoonoses; Mediterranean Area; Leishmania infantum; canine macrophage; RNA-seq; virulence; DH82 cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.