Changes in Macrophage Gene Expression Associated with Leishmania (Viannia) braziliensis Infection

Abstract

Different Leishmania species cause distinct clinical manifestations of the infectious disease leishmaniasis. It is fundamentally important to understand the mechanisms governing the interaction between Leishmania and its host cell. Little is known about this interaction between Leishmania (Viannia) braziliensis and human macrophages. In this study, we aimed to identify differential gene expression between non-infected and L. (V) braziliensis-infected U937-derived macrophages. We deployed a whole human transcriptome microarray analysis using 72 hours post-infection samples and compared those samples with their non-infected counterparts. We found that 218 genes were differentially expressed between infected and non-infected macrophages. A total of 71.6% of these genes were down-regulated in the infected macrophages. Functional enrichment analyses identified the steroid and sterol/cholesterol biosynthetic processes between regulatory networks down-regulated in infected macrophages. RT-qPCR further confirmed this down-regulation in genes belonging to these pathways. These findings contrast with those from studies involving other Leishmania species at earlier infection stages, where gene up-regulation for this metabolic pathway has been reported. Sterol biosynthesis could be an important biological process associated with the expression profile of macrophages infected by L. (V.) braziliensis. Differential transcriptional results suggest a negative regulation of the genetic regulatory network involved in cholesterol biosynthesis.

Leishmania infantum Induces Mild Unfolded Protein Response in Infected Macrophages

“…Later time points were not taken into consideration since the expression of the reference genes diminished significantly starting from 48 h post-infection (Fig 3B). Moreover, a general downregulation of gene expression after 72 h infection has been reported in literature [28,29]. The gene expression analysis showed a significant induction of the ER stress markers DDIT3/CHOP , ATF3 , ATF4 , CEBPB and the autophagy marker MAP1LC3B , both at 6 h and 24 h post-infection; HSPA5 was significantly induced only after 24 h, while CHAC1 did not show any significant variation (Fig 4A).…”

Leishmania donovani induced Unfolded Protein Response delays host cell apoptosis in PERK dependent manner

“…The magnitude of UPR induction during infection was comparatively lower than thapsigargin treatment which gradually decreases at later time points; might be a requirement for spread and progression of infection after successful establishment. Moreover, a general down regulation of gene expression at later stages of infection has been reported in literature [ 48 , 49 ].…”

Changes to cholesterol trafficking in macrophages by Leishmania parasites infection

“…major and L. amazonensis in macrophages of BALB/c mice (Osorio y Fortea et al., ; Rabhi et al., ). However, whether this biological response is universal needs further studies, since, for example, in dendritic leukocytes L. amazonensis did not influence (Lecoeur et al., ), whereas in macrophages derived from human lung lymphoblasts L. viannia braziliensis even lead to downregulation of the expression of genes belonging to steroid and sterol biosynthetic processes (Ovalle‐Bracho, Franco‐Munoz, Londono‐Barbosa, Restrepo‐Montoya, & Clavijo‐Ramirez, ).…”