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

Abstract

Zoonotic visceral leishmaniosis caused by Leishmania infantum 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 L. infantum isolates in their interaction with their different hosts.

Leishmania major Strain-Dependent Macrophage Activation Contributes to Pathogenicity in the Absence of Lymphocytes

“…In contrast, several parasite-specific virulence and survival factors were upregulated in the amastigote of the virulent strain ( 51 ). Strain-mediated induction of differential gene expression (DGE) was also reported recently in canine macrophages infected with Leishmania infantum ( 52 ). Several DEGs are involved in the inflammatory response, cytokine, and chemokine activity.…”

Genomics: Infectious Disease and Host–Pathogen Interaction

“…In parasitic protozoan, a less virulent strain of Leishmania infantum (BOS1FL1) isolated from a canine outbreak in Spain was compared to the reference strain (BCN150) with a canine macrophage infection model by using a transcriptomic approach. Surprisingly, pathways such as phagocytosis and the signal transduction of TNF, MAK, and NFκB were only altered after infection with BOS1FL1 but not with the reference strain, suggesting that low virulence of the BOS1FL1 strain may be due to these mechanisms [ 14 ].…”

“…This Special Issue of the International Journal of Molecular Sciences entitled “Genomics: Infectious Disease and Host –Pathogen Interaction” contains twelve original articles and three reviews that provide new insights into infectious diseases with regard to biofilm formation [ 1 , 2 , 3 ], diagnostics [ 4 ], vaccine development [ 5 ], and host–pathogen interaction [ 6 , 7 ]; these insights are based on genomic [ 8 , 9 , 10 , 11 , 12 ], transcriptomic [ 13 , 14 ], and microbiomic [ 15 ] studies.…”