Relationship of peripheral blood mononuclear cells miRNA expression and parasitic load in canine visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) in humans is a chronic and often fatal disease if left untreated. Dogs appear to be the main reservoir host for L. infantum infection, however, in many regions other canids such as jackals, foxes, wolves and other mammals, such as hares or black rats, have been implicated as wild reservoirs. Most dogs cannot form an effective immune response against this infection, and this could be modulated by small non-coding RNAs, called microRNAs, responsible for post-transcriptional control of gene expression. Here, we evaluated the expression of miRNAs in peripheral blood mononuclear cells (PBMC) of symptomatic dogs naturally infected with Leishmania (L.) infantum (n = 10) and compared to those of healthy dogs (n = 5). Microarray analysis revealed that miR-21, miR-424, miR-194 and miR-451 had a 3-fold increase in expression, miR-192, miR-503, and miR-371 had a 2-fold increase in expression, whereas a 2-fold reduction in expression was observed for miR-150 and miR-574. Real-time PCR validated the differential expression of miR-21, miR-150, miR-451, miR-192, miR-194, and miR-371. Parasite load of PBMC was measured by real-time PCR and correlated to the differentially expressed miRNAs, showing a strong positive correlation with expression of miR-194, a regular positive correlation with miR-371 expression, and a moderate negative correlation with miR-150 expression in PBMC. These findings suggest that Leishmania infection interferes with miRNAs expression in PBMC, and their correlation with parasite load may help in the identification of therapeutic targets in Canine Visceral Leishmaniasis (CVL).

MicroRNAs: Biological Regulators in Pathogen–Host Interactions

“…The initial steps of the inflammatory response occur during the phagocytosis of Leishmania and its establishment inside the phagolysosome and it is able to modulate the immune response by reducing the efficiency of inflammation and the development of an adaptive immune response [52][53][54][55]. Recent studies demonstrated that infections caused by L. amazonensis, L. infantum, L. major, and L. donovani can induce alteration in the miRNA profile from macrophages and dendritic cells of humans, murines, and dogs, thereby implicating the recognition and activation mechanisms of the immune response against parasites [56][57][58][59][60][61][62][63].…”

“…Furthermore, canine visceral leishmaniasis in symptomatic dogs who were naturally infected with L. infantum showed a differential modulation in the expression of miR-150, miR-451, miR-192, miR-194, and miR-371 in PBMCs, which can target genes to regulate the immune response and pathogenesis, such as NF-κB, TNF-α, CD80, and IFN-γ, which are important molecules related to resistance against the disease [62]. The L. infantum infection of human U937 and THP-1-derived macrophages upregulates miR-346, which decreases the mRNA level of genes initially associated with decreased MHC class I and II antigen presentation, TAP1, RFX1, and BCAP31.…”

Leishmania-Host Interactions—An Epigenetic Paradigm

“…Leishmania infection targets cellular miRNA repertoire and the differential miRNA expression is dependent on infecting species (37). A plethora of studies indicate miRNAs as key regulators of disease phenotype in Leishmania -infected cells (27, 30, 32–34).…”

Super enhancer-mediated transcription of miR146a-5p drives M2 polarization during Leishmania donovani infection

“…Recently, small RNA sequencing identified differential enrichment of immune-regulatory microRNAs (miRNAs) in VL patient peripheral blood monocytes (PBMCs) and L. donovaniinfected THP-1 cells [17][18][19]. Muxel et al reported that Leismania amazoniensis infection alters TLR pathway mediators in infected macrophages via modulation of let-7e.…”