Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules

Abstract

Helminths are extraordinarily successful parasites due to their ability to modulate the host immune response. They have evolved a spectrum of immunomodulatory molecules that are now beginning to be defined, heralding a molecular revolution in parasite immunology. These discoveries have the potential both to transform our understanding of parasite adaptation to the host and to develop possible therapies for immune-mediated disease. In this review we will summarize the current state of the art in parasite immunomodulation and discuss perspectives on future areas for research and discovery.

Regulation of immunity and allergy by helminth parasites

“…Fuller accounts of these findings have been published recently in major review articles. [65][66][67] It is perhaps in the context of allergy that the principles and mechanisms of helminth down-modulation have been most clearly established and shown to operate at several levels against both innate and adaptive immunities. Multiple helminth species can, when introduced in to mice, forestall the development of allergic inflammation, 68,69 including H polygyrus [70][71][72] and S mansoni 43,73,74 as well as the filarial parasite Litomosoides sigmodontis.…”

“…102 As these authors note, however, this study does not exclude the likelihood that helminths also directly suppress immune reactions independently of the microbiota, as evidenced by increasing definition of allergy-suppressing proteins released by many parasites, among them H polygyrus itself. 67,103 In both the intestinal tract and the airways, barrier integrity can be physically compromised by helminth parasites, which can initiate a type 2 proto-allergic response (Figure 2). Studies on barrier function in helminth infections of the intestinal tract have documented increased epithelial permeability, 104 which contributes to the "weepand-sweep" mechanism for parasite clearance.…”

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

“…The role of the type 2 immune response in the alteration of the microbiota is particularly important when considering mucus production, as mucus provides a niche for specific bacterial populations and be used as food source by others. Importantly, increased SCFA production in helminth infected mice was associated with changes in the microbial communities (Figure ) . Clostridiales, a bacterial family that includes potent SCFA producers and is able to induce Tregs, have been noted to increase across multiple infection models Interestingly, feeding of mice with SCFAs, or modulation of the SCFA signalling pathways, has been shown to alter the course of DIO and to change insulin resistance .…”

“…Helminth‐based therapies have been used for other inflammatory diseases such as IBD; however, their effects have tended to be subtle, and currently, there is little evidence to support live helminth therapy as a treatment against inflammation‐driven diseases . Instead, most work is currently focused on screening the molecular secretome of helminths as potential therapeutic candidates, with more recent work additionally fuelling interest in investigating the helminth‐altered microbiota as a new avenue for identifying therapeutic metabolites. Together with the expansion of multi‐omics analysis, the microbiota is now considered a gold mine for the discovery of metabolites and their usage as therapies .…”

Macrophages assemble! But do they need IL‐4R during schistosomiasis?

“…Helminths, a huge global burden on public health, induce potent type 2 and immuno‐regulatory networks which can limit the damage these parasites cause . Therefore, studying the immune response during helminth infection and potentially exploiting this information for the development of novel therapeutics has become a field of great interest to the scientific community.…”