Taenia soliumandTaenia crassiceps: miRNomes of the larvae and effects of miR-10-5p and let-7-5p on murine peritoneal macrophages

Abstract

Neurocysticercosis (NCC), a major cause of neurological morbidity worldwide, is caused by the larvae of Taenia solium. Cestodes secrete molecules that block the Th1 response of their hosts and induce a Th2 response permissive to their establishment. Mature microRNAs (miRs) are small noncoding RNAs that regulate gene expression and participate in immunological processes. To determine the participation of Taenia miRs in the immune response against cysticercosis, we constructed small RNA (sRNA) libraries from larvae of Taenia solium and Taenia crassiceps. A total of 12074504 and 11779456 sequencing reads for T. solium and T. crassiceps, respectively, were mapped to the genomes of T. solium and other helminths. Both larvae shared similar miRNome, and miR-10-5p was the most abundant in both species, followed by let-7-5p in T. solium and miR-4989-3p in T. crassiceps, whereas among the genus-specific miRs, miR-001-3p was the most abundant in both, followed by miR-002-3p in T. solium and miR-003a-3p in T. crassiceps. The sequences of these miRs were identical in both. Structure and target prediction analyses revealed that these pre-miRs formed a hairpin and had more than one target involved in immunoregulation. Culture of macrophages, RT-PCR and ELISA assays showed that cells internalized miR-10-5p and let-7-5p into the cytoplasm and the miRs strongly decreased interleukin 16 (Il6) expression, tumor necrosis factor (TNF) and IL-12 secretion, and moderately decreased nitric oxide synthase inducible (Nos2) and Il1b expression (pro-inflammatory cytokines) in M(IFN-γ) macrophages and expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M(IL-4) macrophages. These findings could help us understand the role of miRs in the host–Taenia relationship.

Taenia solium microRNAs: Potential Biomarkers and Drug Targets in Neurocysticercosis

“…These five miRNAs account for ~90% of miRNA expression [17]. These miRNAs and miR-4989 were also highly expresses in Taenia solium cysticerci [27]. Coincidentally, in other reports of small RNAs from cestodes that used the same methodology for miRNA discovery, miR-10, let-7, miR-71 and bantam were the most highly expressed, suggesting important functions in cestode biology [20,21,23,24].…”

“…Already knowing that the more abundant miRNAs (miR-10-5p, let-7-5p) putatively have target genes of immune response and that macrophages in murine cysticercosis promote Th1 or Th2 responses it was demonstrated that synthetic miR-10-5p and let-7-5p were internalized into the cytoplasm of murine peritoneal macrophages in vitro [27]. Interestingly, the down regulation of the expression of pro-inflammatory cytokines, such as Il6, Il1b, and TNF, IL-12, was reported when activated macrophages were incubated with IFN-γ and miR-10-5p or let-7-5p.…”

miR-10c Facilitates White Spot Syndrome Virus Infection by Targeting Toll3 in Litopenaeus vannemei

“…In mice, the miR-10a targets Prdm1 gene to suppress the production of IL-10 in CD4 + T cells, playing important roles in regulation of intestinal homeostasis and in pathogenesis of autoimmune diseases ( 42 ). The parasites Taenia solium and T. crassiceps produce an abundance of miR-10-5p, which is important for establishment of immunosuppressive mechanisms in the host by acting on host cells to regulate expression of proinflammatory cytokines in macrophages M(IFN-γ) and anti-inflammatory cytokines in macrophages M(IL-4) ( 43 ). As the novel identified miRNA, miR-10c has a base different from known miR-10 and miR-10a in the seed region, and its targeting genes may be different from those of miR-10.…”

Identification and Expression Profiling of Circulating MicroRNAs in Serum of Cysticercus pisiformis-Infected Rabbits

“…The most abundant miR-10-5p and let-7-5p in Taenia solium and Taenia crassiceps characterized immunosuppressive effects on murine peritoneal macrophages, which strongly decreased the expression of interleukin 6 (IL-6), tumor necrosis factor (TNF) and interleukin (IL-12) secretion. They also moderately decreased nitric oxide synthase inducible (NOS2) and Il1b expression (pro-inflammatory cytokines) in M (IFN-γ) macrophages, expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M (IL-4) macrophages [37]. miRNA let-7-5p from C. pisiformis exosomes has been reported to decrease M1 phenotype expression while promoting polarization to the M2 phenotype through inhibition of the expression of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ.…”