Background: Autoimmune diseases are characterised by a T_H1-type immune response, mediated by inflammatory-M1 macrophages, whereas regulatory-M2 macrophages promote the T_H2-type immune response to allergens or parasitic worm infections. Understanding how each macrophage phenotype is activated could lead to novel therapeutic approaches. Micro(mi)RNAs are small non-coding RNAs which exhibit post-translational/post-transcriptional mechanisms to regulate the differentiation of immune cells. However, few studies have investigated the role of miRNAs in the activation of macrophage phenotypes in vivo.

Hypothesis: Parasitic infections alter host miRNAs, stimulating the activation of M2 macrophages, independently of Th2 cytokines.

Methods: Using a murine model of a parasitic infection, we established a correlation between the expression of miRNAs and the changing phenotype of macrophages over time during a T­_H2 immune response. Peritoneal macrophages, isolated from Balb/c mice at various time points over a 5 day period of infection with Fasciola hepatica, were analysed for the abundance of miRNA by RNAseq analysis, where the entire expression profile of all miRNAs in peritoneal macrophages at various time points after infection was obtained. From this, the temporal profile of expression of the top 5 most abundant, along with various mRNA, was validated by qPCR. Additionally, cytokine levels within the peritoneal lavage fluid, were measured by ELISA.

Results: Two significant patterns of miRNA expression emerged; a peak at 6h which returned to baseline levels by 12h; a gradual increase in expression reaching a maximum at day 5. The latter profile matched the expression of mRNA for M2 macrophage markers, but occurred prior to the production of T_H2-type cytokines.

Conclusion: Specific miRNAs are altered after infection and some correlate to the activation of M2 macrophages. Further investigation is required to demonstrate a mechanistic role for these miRNAs in the regulation of macrophage differentiation.