Regulation of immunity and allergy by helminth parasites

Abstract

There is increasing interest in helminth parasite modulation of the immune system, both from the fundamental perspective of the “arms race” between host and parasite, and equally importantly, to understand if parasites offer new pathways to abate and control untoward immune responses in humans. This article reviews the epidemiological and experimental evidence for parasite down‐regulation of host immunity and immunopathology, in allergy and other immune disorders, and recent progress towards defining the mechanisms and molecular mediators which parasites exploit in order to modulate their host. Among these are novel products that interfere with epithelial cell alarmins, dendritic cell activation, macrophage function and T‐cell responsiveness through the promotion of an immunoregulatory environment. These modulatory effects assist parasites to establish and survive, while dampening immune reactivity to allergens, autoantigens and microbiome determinants.

COVID-19 Lethality in Sub-Saharan Africa and Helminth Immune Modulation

“…For controlling the helminth infections, the adaptive immunity of the host usually develops type 2 immune responses, including the development of Th2 cells and the release of cytokines such as IL-4, IL-5, and IL-13 (16). This host-helminth interaction has, at least, two additional outcomes: (i) the classical and best-known down-regulation of type Th1 and type Th17 responses (and its related cytokines IL-12, IFN-γ, IL17, IL-23, TNF-α) by the Th2 cytokines (16,17) and (ii) the helminths limitation of both host type1 and type 2 responses by enhancing FOXP3+ T regulatory cells, B regulatory cells and alternatively activated macrophages (AAMs) activities, which together cause the release of regulatory cytokines such as IL-10 and transforming growth factor (TGF-β) (18).…”

“…The modulation by helminths of the immune responses of their hosts has relevant clinical and epidemiological consequences: increased susceptibility to some infections, decreased frequency and intensity of allergic, autoimmune and inflammatory diseases, inadequate responses to vaccines and, as is possible in the case of SARS-CoV-2 infection, may inhibit the inflammatory processes that characterize infection by other microorganisms (17).…”

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities

“…The mechanisms by which parasitic helminths regulate inflammation and metabolism are diverse and complex and have been reviewed extensively [11][12][13][14][15]. Helminths are potent drivers of T helper type 2 (T H 2) immune responses, characterized by eosinophilia, mast cell mastocytosis, type 2 innate lymphoid cells (ILC2s), tuft cells, and mucus production.…”

Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

“…Concomitantly, regulatory T cells are stimulated to produce suppressive cytokines which act on B cells to switch to IgG4 production. A state of tolerance is developed characterized by a profound anti‐inflammatory effect . The precise role played by antibodies and the functional properties of antibody in these interactions remain little investigated.…”