Helminth Immunomodulation in Autoimmune Disease

Abstract

Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating "talents" of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

Keywords: autoimmunity; excretory/secretory products; helminthic therapy; immunomodulation; immunotherapy.

Figure 1

Helminth excretory/secretory (ES) products effect on host immune cells. Infection with parasitic worms causes the host immune system to polarize into a Th2 response (preventing Th1 or Th17 immune response) characterized by Th2 cytokines. Helminth ES products can cause the differentiation of macrophages toward the M2 phenotype, resulting in a Th2 immune response. ES products can also prevent dendritic cell synthesis of pro-inflammatory cytokines and promote the production of immunoregulatory molecules such as IL-10 and TGFβ. A regulatory T cell (Treg) phenotype is also induced, promoting the protection/suppression of inflammation produced by a Th1 autoimmune disease. Myeloid-derived suppressor cells (MDSC) function as immunoregulators, producing reactive oxygen/nitrogen species that inhibit the function of T cells.