Regulation of the host immune system by helminth parasites

They may be called parasites, but we may owe helminth worms a great deal of appreciation.  At least, that’s what Dr Maizels and McSorley write in this month’s issue of the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol 2016; 138(3): 666-675).  To those who are unaware, there are only about a dozen or so species of helminths that commonly infect human beings, but they affect more than 2 billion people worldwide.  Their wide prevalence is a testament to the fact that they can evade host defenses and establish niches from themselves within our bodies.  Learning about how they do this can provide valuable insights about how our immune system works.

They do this through many different ways.  T-cells from helminth-infected asymptomatic humans show an increase in IL-4, IL-10, and TGF-beta over IL-17 and Interferon-gamma, suggesting that parasites skew our T-cells in a way that reduces the immune system’s ability to clear helminths.  In particular, the production of IL-10 correlates with the proliferation of regulatory T-cells, which in turn drive the body to produce IgG4 instead of pro-allergic IgE antibodies.  Interestingly, when helminths are cleared away by drug treatment, IgG4 levels decrease, which suggests that it is the helminths that are driving this movement.  Very broadly, this affects a host of other cells within the body, including macrophages, dendritic cells, and B-cells, which also seem to become more tolerating of these helminths.

The end-result of these changes is a mixed bag.  Helminths prevent the body from creating polyclonal responses, leading to decreased defense against pathogens like mycobacterium tuberculosis, and compromising the effect of childhood vaccines.  They also increase the risk of developing cancer, change metabolic processes (and maybe even protect against diseases like diabetes mellitus), and alter the bacteria that make up our gut microbiome.  Not surprisingly, at least in mice, helminth infection attenuates allergic responses as well. 

These insights are incredibly important, not only because they allow us to understand the immune system in a clearer manner, but also because research in this area holds the promise of creating new therapies that mimic the parasite molecules to treat a number of inflammatory diseases.