MicroRNA‐mediated regulation of immune responses to intestinal helminth infections

Abstract

Intestinal helminth infections are highly prevalent in the developing world, often resulting in chronic infection and inflicting high host morbidity. With the emergence of drug-resistant parasites, a limited number of chemotherapeutic drugs available and stalling vaccine efforts, an increased understanding of antihelminth immunity is essential to provide new avenues to therapeutic intervention. MicroRNAs are a class of small, nonprotein coding RNAs which negatively regulate mRNA translation, thus providing finite control over gene expression in a plethora of biological settings. The miRNA-mediated coordinated control of gene expression has been shown to be essential in infection and immunity, in promoting and fine-tuning the appropriate immune response. This review gathers together and discusses observations of miRNA-mediated effects on the immune system and the subsequent impact on our understanding of antihelminth immunity.

Can Parasitic Worms Cure the Modern World’s Ills?

“…Rather they comprise a wide range of biologically active molecules including glycans [20] and microRNAs [20,21,126,127] as well as small molecule metabolites, exemplified by the immunoregulatory actions of fluke peptides, eicosanoids (Schistosoma mansoni), ascaroside lipids and short chain fatty acids (SCFA) generated by Toxocara canis, Ostertagia circumcincta and Haemonchus contortus [20]. Although many of these agents are released in free-form, the discovery of helminth-derived exosomes/extracellular vesicles containing varied cargo mixes [21,[126][127][128] has generated much interest in their function. Those containing immunoregulatory microRNAs have been identified from Fasciola hepatica, Heligomosomides polygyrus, Litomosoides sigmodontis, Dicrocoelieum dendriticum and Dirofilaria immitis, which following dissection of their roles could be exploited therapeutically [21].…”

Anisakis pegreffii impacts differentiation and function of human dendritic cells

“…Generally, the immune response to helminth is triggered by damage to the epithelial cells with secretion of alarmins (TSLP, IL‐33 and IL‐25) and activation of antigen‐presenting cells such as dendritic cells (DCs), innate lymphoid cells 2 (ILC2) and macrophages. This drives an overall activation and amplification of Th2 cell differentiation, subsequent class switching of B cells (IgA, IgE and IgG) and a promotion of the migration of Th2 cells back to the site of infection . Thus, the activation and the modulation of the human immune response are strictly dependent on the functions of APCs engaged by the helminth pathogens.…”

“…This drives an overall activation and amplification of Th2 cell differentiation, subsequent class switching of B cells (IgA, IgE and IgG) and a promotion of the migration of Th2 cells back to the site of infection. 16,17 Thus, the activation and the modulation of the human immune response are strictly dependent on the functions of APCs engaged by the helminth pathogens.…”

microRNAs—key players in host–parasite interactions

“…Host immune responses to infection with helminth and protozoan parasites are highly complex, and not surprisingly, miRNAs play essential roles in coordinating and fine‐tuning many aspects of the mammalian immune response . Details of miRNA‐mediated regulation of immune responses to gastrointestinal (GI) nematodes and to Cryptosporidium are reviewed in this issue. Immunity and expulsion of GI nematodes involve a range of cell types and cytokines.…”

“…Immunity and expulsion of GI nematodes involve a range of cell types and cytokines. The importance of miRNAs in regulating these responses is demonstrated by genetic deletion of the miRNA processing enzyme Dicer or of specific miRNA loci, as summarized by Entwistle and Wilson . Loss of Dicer alters the intestinal architecture and results in increased susceptibility to infection with the GI nematode Trichuris muris .…”