Student guest post by Shylo Wardyn
“Of all the parasites I’ve had over the years, these worms are among the… hell, they are the best”.
Was Fry from the animated show ‘Futurama’ right in his assessment of worms being good for him? Did he know something about parasitic worm infections that I was unaware of? Well, in the show, his parasites were doing remarkable things for his body, but does this translate to real life at all? Some people think so. Altman reviews the idea that over evolutionary time, our ancestors were infected with all sorts of parasites and this led to an interaction between the worm gene products and the immune system. These interactions led to modulation of dendritic cells and establishment of T-cell networks. It has been hypothesized that in an environment without these interactions, as is the case for most people living in “Westernized” countries, there is a loss of the ‘fine tuning’ of the adaptive immune system.
In another review, Jackson et al. discuss how this mechanism could have co-evolved. It is generally believed that the T helper cell type 2 (Th2) evolved to counter infections with parasitic worms. These cells are activated in response to parasitic worm infection, which leads to a large regulatory T cell response. Our response to worms seems to involve an immune response that is less inflammatory than our response to microbes, and it also takes much longer to reach the peak of effectiveness. This is due in large part to an initial systemic suppression of innate and adaptive immunity in the host. This is likely caused by regulatory CD4+ and CD25+ T cells producing suppressive cytokines or other suppressor T cell subsets. Anti-inflammatory responses are also caused by alternatively activated macrophages. These macrophages secrete anti-inflammatory cytokines and express genes whose functions relate to wound healing and repair. Therefore, being infected with parasitic worms leads to a down-regulation of proinflammatory responses, while allowing mechanisms for wound repair and a controlled development of the Th2 response. This Th2 and T regulatory response is beneficial for both the worm and the host. For us, the regulated Th2 response is less costly than the generation of a strong immune response, which often can be detrimental to our own cells. For the parasites, they are able to survive the initial immune response and therefore reproduce, while later parasites would not be able to survive the developed immune response.
The overall thought is that since parasitic worm infections are ubiquitous in mammals and have been since mammals first evolved, there would be a positive selective pressure for those individuals whose immune systems respond well to worm infections. Our immune systems may have been selected to anticipate a chronic exposure to Th2 and T regulator inducing pathogens. Since our ancestors were chronically infected by worms, their immune systems would have developed to work well in this context, while not necessarily working as well in the absence of worms. This scenario may explain why in some cases the immune system goes haywire in populations that are free from parasitic worms.
So is there any strong evidence linking parasites with populations free from allergies and autoimmune diseases? There have been many ecological studies which show an inverse correlation between the parasite load and allergy level for a particular region. Does this prove anything? Not really, the data is simply correlative. There have been other studies showing that treatment of worm infections is accompanied by an increase in skin test reactivity to allergens and IgE antibody levels. It appears that in the absence of worms, the immune system overreacts to allergens to which it normally wouldn’t mount a response in the presence of worms. This gives us a better idea about the link between parasitic worms and immune responses. While the evidence is still shaky, it is biologically plausible that the lack of worms in our environment has led to the massive increase in the amount of immune related diseases, such as asthma, multiple sclerosis, type 1 diabetes, and general allergies. However, the immune system is incredibly complex, as are those diseases, and I’ve barely scratched the surface of it for this topic. So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm. It does make for an interesting hypothesis (and Futurama episode) though and should be researched more thoroughly.
Altmann D. M. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology, 126(1); 1-2.
Jackson J. J., Friberg I.M., Little S. and Bradley J. E. (2008). Review series on helminths, immune modulation and the hygienehypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, 126(1); 18-27.
Weiss S.T. (2000). Parasites and asthma/allergy: What is the relationship? Journal of Allergy and Clinical Immunology, 105(2); 205-210.