Micro(RNAs)managing Macrophage Polarization During Schistosomiasis

Article history: Received 2 November 2016 Accepted 2 November 2016 Available online 8 November 2016 and development has become an intense area of research (Zhu et al., 2014), the role of host miRNAs in shaping immune responses against these parasites has been poorly characterized. In a previous study He and coworkers performed a miRNA microarray on livers from S. japonicum-infected mice and identified miRNA-146 as one of several strongly upregulated miRNAs in response to infection (He et al., Infectionswith parasitic helminths of the genus Schistosoma are considered one of the most socioeconomically devastating parasitic diseases, with hundreds of millions of people infected worldwide. These infections can result in significant morbidity primarily due to parasitederived eggs that accumulate in tissues, such as the liver (in the case of S. mansoni and S. japonicum infection), where they drive inflammation, tissue damage and fibrosis (Pearce and MacDonald, 2002). Macrophages have been shown to play a key modulatory role in this egginduced immunopathology. Before the onset of egg-laying by the adult worms, the host immune response is characterized by a T helper 1 (Th1) response, which through the secretion of IFN-γ promotes the differentiation of macrophages towards a more pro-inflammatory classically activated phenotype (‘M1’). Upon egg deposition a potent type 2 immune response is triggered, in which Th2 cells and Type 2 cytokinedriven alternatively activated macrophages (‘M2’) predominate. This M2 phenotype of macrophages is crucial for the host to survive acute schistosomiasis, by keeping Type 1 inflammatory responses, including those mediated by M1macrophages, in check that would otherwise result in potentially lethal tissue-damage. Moreover, M2macrophages are involved in granuloma formation and induction of fibrosis around eggs trapped in tissues, which is thought to be an important host protective mechanism against egg-driven pathology (Barron and Wynn, 2011). This illustrates the importance of a tight regulation of macrophage polarization during schistosomiasis and disease outcome. However, the molecular mechanisms that control macrophage polarization in egg-affected tissues are still not fully understood. In the current issue He and coworkers provide for the first time support for an important role for a specificmicroRNA (miRNA),miRNA-146, in regulating the balance between M2 and M1 macrophage polarization during S. japonicum-induced hepatic schistosomiasis (He et al., 2016). miRNAs are small ubiquitously expressed non-coding RNAs, that regulate gene expression at the post-transcriptional level through RNA silencing and thereby play important roles in various aspects of cell biology, including regulation of the functional properties of immune