Helminth Regulation of Immunity

Abstract

By reputation, the parasite is a pariah, an unwelcome guest. Infection with helminth parasites evokes stereotypic immune responses in humans and mice that are dominated by T helper (Th)-2 responses; thus, a hypothesis arises that infection with helminths would limit immunopathology in concomitant inflammatory disease. Although infection with some species of helminths can cause devastating disease and affect the course of microbial infections, analyses of rodent models of inflammatory disease reveal that infection with helminth parasites, or treatment with helminth extracts, can limit the severity of autoinflammatory disease, including colitis. Intriguing, but fewer, studies show that adoptive transfer of myeloid immune cells treated with helminth products/extracts in vitro can suppress inflammation. Herein, 3 facets of helminth therapy are reviewed and critiqued: treatment with viable ova or larvae, treatment with crude extracts of the worm or purified molecules, and cellular immunotherapy. The beneficial effect of helminth therapy often converges on the mobilization of IL-10 and regulatory/alternatively activated macrophages, while there are reports on transforming growth factor (TGF)-β, regulatory T cells and dendritic cells, and recent data suggest that helminth-evoked changes in the microbiota should be considered when defining anticolitic mechanisms. We speculate that if the data from animal models translate to humans, noting the heterogeneity therein, then the choice between use of viable helminth ova, helminth extracts/molecules or antigen-pulsed immune cells could be matched to disease management in defined cohorts of patients with inflammatory bowel disease.

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 + Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

“…The adoptive transfer of these M (HdAg) cells inhibited DSS-induced colitis, demonstrating a novel aspect by which helminth-derived molecules could suppress intestinal inflammation. It is apparent that infection with viable helminth parasites, treat- ment with a variety of helminth extracts/antigens, and delivery of either immune cells retrieved from infected individuals or immune cells educated in vitro with helminth antigens all have the capacity to block inflammatory disease (61). The challenge is to define the immunological regulation associated with each of these approaches to suppress inflammation and determine the optimal means to translate this knowledge to the treatment of inflammatory disease.…”

Helminths in the gastrointestinal tract as modulators of immunity and pathology

“…If a chronic infection is established over the succeeding months or years, the host response becomes essentially immunomodulatory and is primarily mediated by regulatory cells (1, 44, 50, 161) and anti-inflammatory cytokines (e.g., IL-10 and TGF-β) to assure that low levels of helminths are tolerated and immune homeostasis prevails. While this vignette is, of course, oversimplified, it well illustrates the alternative modes of antihelminth immune responsiveness and is important in considering whether immune modulation is differentially evoked during different phases of infection (45, 97). …”

A Critical View of Helminthic Therapy: Is It a Viable Form of Treatment for Immune Disorders under the Category of Inflammatory Bowel Disease?

“…reference was the "hygiene hypothesis", stating that a helminth could provide some type of protection against concomitant disease. These two hypotheses combined could explain why the helminth has been able to coevolve with the human species (Lopes et. al ., 2016).…”

“…presented these three forms of treatment for colitis: ingestion of viable ova or larvae of a helminth, use of crude helminthic extracts, and cellular immunotherapy. The most common type of helminthic therapy is through ingestion of viable ova or larvae, and through comparison of animal and human models it proves to be successful (Lopes et. al ., 2016 (Lopes et.al ., 2016).…”

“…al ., 2016 (Lopes et.al ., 2016). The use of these extracts negates the concerns of using live parasites for treatment of a patient with ulcerative colitis (Lopes et. al ., 2016).…”