A life without worms

Abstract

Worms have co-evolved with humans over millions of years. To survive, they manipulate host systems by modulating immune responses so that they cause (in the majority of hosts) relatively subtle harm. Anthelminthic treatment has been promoted as a measure for averting worm specific pathology and to mitigate subtle morbidities which may include effects on anaemia, growth, cognitive function and economic activity. With our changing environment marked by rapid population growth, urbanisation, better hygiene practices and anthelminthic treatment, there has been a decline in worm infections and other infectious diseases and a rise in non-communicable diseases such as allergy, diabetes and cardiovascular disease. This review reflects upon our age-old interaction with worms, and the broader ramifications of life without worms for vaccine responses and susceptibility to other infections, and for allergy-related and metabolic disease. We touch upon the controversy around the benefits of mass drug administration for the more-subtle morbidities that have been associated with worm infections and then focus our attention on broader, additional aspects of life without worms, which may be either beneficial or detrimental.

Keywords: Allergy; Anthelminthic; Helminths; Infectious diseases; Metabolic disease; Vaccines.

Figure 1.

Interactions between helminths and the host immune system, and the impact on bystander responses. Red arrows and blue lines denote positive and suppressive effects, respectively. Helminth migration in the host results in tissue injury, resulting in release of Damage Associated Molecular Patterns (DAMPs) and alarmins. DAMPs and alarmins are involved in the initial activation of eosinophils, type 2 innate lymphoid cells (ILC2) and antigen presenting cells (APCs) such as dendritic cells (DCs), which then mediate further inflammation in the host. However, some helminth secretory products can suppress alarmin release and DC maturation, and some helminth enzymes degrade DAMPs. Helminths also interfere with APC activities, promoting an alternative activation phenotype, which results in production of large amounts of IL-10 and TGFβ. These cytokines downmodulate eosinophil, ILC2 and DC responses, and promote lymphocyte hyporesponsiveness involving regulatory lymphocytes. Helminth interaction with host immunity has spillover effects on responses to bystander antigens. For instance, helminth infections may result in impaired immune responses to vaccines and communicable diseases, although specific helminth molecules may actually have enhancing effects. Likewise, there is evidence for both inverse and positive helminth-allergy associations, although any notable effects on metabolic conditions have been beneficial. DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; HMGB1: High Mobility Group Box 1.

Figure 2.

Is ‘de-worming’ good for us?