View source for The effects of helminths on the immune system

{{Breadcrumb|[[Effects_of_helminthic_therapy|Effects of helminthic therapy]]}}
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The effect that helminths have on the immune system is complex and more a case of subtle modulation (balancing or quieting) than of suppression. This is achieved by employing an orchestra of chemicals that are excreted/secreted by the worms with the primary intention of keeping them and their host alive and well for as long as possible. The benefits derived by the host as a result of this activity include a reduction of inflammation and the prevention of allergy and autoimmune disease.

What is known about what helminths do is summarised as follows.

{{Quote|indent}}Helminths, as long-lived parasites, are remarkable for their ability to manipulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/24749722  Helminths in the hygiene hypothesis: sooner or later?]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/21610741  Diversity and dialogue in immunity to helminths.]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/12949497  Immune regulation by helminth parasites: cellular and molecular mechanisms.]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/27172808  Parasitic helminth infections and the control of human allergic and autoimmune disorders.]</ref> Immunomodulation by parasitic helminths is a general phenomenon that is conserved across species, classes, and even phyla.<ref name="SecretoryProducts">[http://www.ncbi.nlm.nih.gov/pubmed/24704440  Secretory products of helminth parasites as immunomodulators.]</ref> Therefore, parasitic infections are a major theme in the hygiene hypothesis. Allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms.<ref Name="AutoimmuneTag">[http://www.ncbi.nlm.nih.gov/pubmed/14755074  Regulation of allergy and autoimmunity in helminth infection.]</ref> There are strong epidemiological evidences to support the premise that the dramatic increase in atopic disease in the developed world is a direct consequence of the eradication of helminth infections.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/24712468  Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases.]</ref> At least some helminthes seem to have antiallergic or anti-inflammatory effects in humans. Experimental evidences have also shown the significant suppression for the development of airway hyperresponsiveness (AHR) in mice infected with numerous helminths, including blood fluke Schistosoma japonicum,<ref>[http://www.ncbi.nlm.nih.gov/pubmed/18654798  Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice.]</ref> filaria Litomosoides sigmodontis,<ref>[http://www.ncbi.nlm.nih.gov/pubmed/18209076 Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model.]</ref> nematode Heligmosomoides polygyrus,<ref>[http://www.ncbi.nlm.nih.gov/pubmed/16275759  Suppression of allergic airway inflammation by helminth-induced regulatory T cells.]</ref> and Nippostrongylus brasiliensi.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/15039389  Helminth infection modulates the development of allergen-induced airway inflammation.]</ref> These mice show attenuated airway inflammation with reduced infiltration of eosinophilia in the BAL and lung and allergen-specific IgE in sera. Many studies have also demonstrated that helminth infections lower the risk of autoimmunity. Experimental studies have also shown protective effects of helminth infections in animal models of autoimmunity. Surprisingly, helminths have been shown to suppress various types of autoimmune disease, such as collagen-induced arthritis, experimental autoimmune encephalomyelitis, and type 1 diabetes in murine models as reviewed recently.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/20169100  Parasitic helminths: new weapons against immunological disorders.]</ref> Helminth infections might be beneficial to the induction of multiple regulatory mechanisms, including various regulatory cell populations, inhibitory receptors, blocking antibodies, and two prominent cytokines: IL-10 and TGF-β.<ref name="SecretoryProducts"></ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/14755073  Helminth infections and allergic diseases: from the Th2 paradigm to regulatory networks.]</ref> Thus, it is not surprising that helminths can modulate immunopathology, whether in the context of allergic inflammation or autoimmune disease, either directly or indirectly.<ref Name="AutoimmuneTag"></ref> (Source)<ref>[http://www.ncbi.nlm.nih.gov/pubmed/27563682  Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis.]</ref>{{Quote|/indent}}

However, we need to bear in mind that understanding of exactly ''how'' helminths produce these effects is still limited. As Elliott & Weinstock have said,

{{Quote|indent}}In most circumstances, little is known regarding the molecular signals exchanged between helminth and host to mediate this process. Even less is known about which helminth products influence disease and how they work.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/22239614 Helminth-host immunological interactions: prevention and control of immune-mediated diseases.]</ref>{{Quote|/indent}}

People considering the use of helminthic therapy are frequently concerned that the treatment might not be appropriate for them depending on whether they have a condition known to be associated with a Th1 or a Th2 response,<ref>[http://en.wikipedia.org/wiki/Th1_cell Th1/Th2 Model for helper T cells]</ref> but parasitic infections increase the population of regulatory T-cells, or TREGs,<ref>[http://maizelsgroup.biology.ed.ac.uk/regulatory-t-cells-parasite-infection Regulatory T cells in Parasite Infection]</ref> which control the excesses of ''both'' Th1 and Th2 cells, and the extracellular vesicles secreted by many nematodes generate potent suppression of ''both'' type 1 and type 2 immune-response-associated molecules.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/28538175 Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity]</ref> 

{{Quote|indent}}We show here that the local cytokine response to TSO treatment included upregulation of not only Th2 and regulatory cytokines and transcription factors but also Th1/Th17 cytokines.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/28602842 Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer]</ref>{{Quote|/indent}}

Furthermore, helminth infection can result in the production of hybrid Th2/1 cells which express both Th2 and Th1 cytokines.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/28676845 Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells]</ref> 

As a result of these, and perhaps other yet-to-be-identified means, helminths are able to ameliorate both allergies ''and'' autoimmune diseases. 

Another common concern is that helminthic therapy might reduce a host’s ability to fight other types of infection but, far from making the immune system lazy or less effective, helminths actually make it smarter.

{{Quote|indent}}People who host helminths can still mount an inflammatory attack on pathogens, but they don't set off self-destructive immune bombs against harmless substances or their own cells. (William Parker, Duke University)<ref>[http://www.menshealth.com/health/immune-system-worms The New (Ancient) Cure for Immune Disorders]</ref>{{Quote|/indent}}

=== See also ===

* [https://www.ncbi.nlm.nih.gov/pubmed/29262347 Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection]

* [[Helminthic therapy and infectious diseases | '''Helminthic therapy and infectious diseases''']]
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== References ==