Abstract
Parasitic helminths are among the most pervasive pathogens of the animal kingdom. To complete their life cycle, these intestinal worms migrate through host tissues causing significant damage in their wake. As a result, infection can lead to malnutrition, anemia and increased susceptibility to co-infection. Despite repeated deworming treatment, individuals living in endemic regions remain highly susceptible to re-infection by helminths, but rarely succumb to excessive tissue damage. The chronicity of infection and inability to resist numerous species of parasitic helminths that have co-evolved with their hosts over millenia suggests that mammals have developed mechanisms to tolerate this infectious disease. Distinct from resistance where the goal is to destroy and eliminate the pathogen, disease tolerance is an active process whereby immune and structural cells restrict tissue damage to maintain host fitness without directly affecting pathogen burden. Although disease tolerance is evolutionary conserved and has been well-described in plant systems, only recently has this mode of host defense, in its strictest sense, begun to be explored in mammals. In this review, we will examine the inter- and intracellular networks that support disease tolerance during enteric stages of parasitic helminth infection and why this alternative host defense strategy may have evolved to endure the presence of non-replicating pathogens and maintain the essential functions of the intestine.
Highlights
Parasitic helminths include a diverse group of intestinal worms that are one of the most successful pathogens of the animal kingdom
Parasitism has been thought to be solely detrimental: the parasite benefits at the expense of host health, with only one “winner” emerging from this interaction. Developing resistance to these invaders was the conceptual framework that led to great advances in understanding type 2 immunity and its relation to anti-helminth immunity
Given that helminth infection almost universally activates type 2 immune pathways yet does not necessarily lead to resistance or protective immunity to re-infection suggests that tolerance is an important, mode of host defense to this unique class of parasitic infection
Summary
Parasitic helminths include a diverse group of intestinal worms that are one of the most successful pathogens of the animal kingdom. This work has been recently supported and expanded upon in human vascular disease [26], a zebrafish model of tissue regeneration [27] and mouse models of acute skin [28], liver [29], and muscle injuries [30] where IL-4/IL-13 signals promote clearance of cellular debris and tissue healing by structural cells and AAMacs These results suggest that type 2 immunity is part of a conserved tissue repair program co-opted to limit tissue damage and support barrier integrity during helminth infection. Early responses to helminth infection may simultaneously involve components of a type 1 and type 2 immune response that limit microbial invasion during a helminth-induced barrier breach and promote tissue repair/regeneration and limit tissue damage, yet have minimal effect on parasite burden
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