Can a gut helminth parasite influence Th2 inflammatory responses in the skin?

Abstract

Helminth parasites are one of the most common infectious agents of humans and cause significant health and economic burdens in the countries they are endemic in, making elimination an important goal. However, epidemiological studies have suggested an inverse correlation between the incidences of infections by helminth parasites in humans and autoimmune and allergic disease prevalence worldwide; it is thought the eradication of parasites in more affluent countries through improved hygiene is an important factor for the increasing incidence of autoimmune and allergic diseases encountered in the Western world.

A Th2 immune response is central in providing immunity against helminth parasites, while suppressing T helper (Th) 1/Th17-mediated inflammation and inducing wound repair mechanisms. Helminths have developed strategies to directly regulate the immune response against them to ensure their own survival. Experimental evidence has demonstrated helminths are also able to dampen inflammatory bystander immune responses in their host, via induction of regulatory mechanisms such as regulatory T cells. These studies have focused primarily on the suppression of food and airway allergies in mouse models and there is limited data on the effect of helminth parasites on skin allergy e.g. atopic dermatitis.

Atopic dermatitis (AD) is a chronic/chronically relapsing Th2 inflammatory skin condition, characterized by skin lesions, dry itchy skin and impaired skin barrier function. This is believed to allow the entrance of other allergens into the body more easily, leading to sensitization and initiation of other allergies later in life, a process termed the ‘Allergic March’. With the increased incidence of allergy in the Western world, it is desirable to find new therapies to suppress AD and the onset of the allergic march.

During my Masters, I have investigated whether the gut-dwelling mouse parasite Heligmosomoides polygyrus was able to suppress Th2 responses induced in skin tissue using two different allergy models: 1) intradermal injection (ID) of whole mashed-up house dust mite (HDM), which induces Th2 inflammatory responses, and 2) topical application of the chemical hapten dibutyl phthalate-fluorescein isothiocyanate (DBP-FITC), mimicking allergic responses seen in AD. The results show that H. polygyrus induces interleukin (IL)-4 production in tissues distal to the gut, including the ear skin tissue, mainly from cluster of differentiation (CD) 4⁺ T cells. Furthermore, helminth infection was able to suppress Th2-mediated inflammation in the skin in both house dust mite and DBP-FITC models, coinciding with an increase in the proportions of regulatory T cells (Tregs) in skin-associated lymph nodes (LNs). This research further demonstrates the potential use of helminth parasites, or their products, as a therapy for allergic diseases, including those of the skin.