Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

Abstract

Purpose of Review It is well established that T helper type 2 (TH2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH2 cell polarization. In addition to the adaptive compartment, emerging studies are better defining the innate immune pathways needed to promote TH2 cell responses. Given the recent and substantial growth of this field, the purpose of this review is to highlight recent studies defining the innate immune events that promote immunity to helminth parasites and allergic inflammation. Recent Findings Emerging studies have begun to elucidate the importance of cytokine alarmins such as thymic stromal lymphopoietin (TSLP), IL-25 (IL-17E) and IL-33 in promoting type 2 immunity and inflammation following helminth challenge or exposure to allergens. Specifically, recent reports have begun to define the complex cellular networks these alarmins activate and their contribution to type 2 immunity and inflammation. Summary Our increased understanding of the pathways that regulate type 2 cytokine-mediated immunity and inflammation have revealed novel therapeutic targets to treat both helminth infections and allergic disease states.

First Responders: Innate Immunity to Helminths

“…In contrast to helminth infections, type 2 inflammation, when uncontrolled, is also known to promote inflammation associated with allergies and asthma. Therefore, studies investigating the mechanisms that regulate allergic responses have helped to inform our understanding of helminth-induced inflammation[8]. Although the purpose of this article is to highlight recent studies describing the initiation of host-protective responses following helminth challenge, we have also highlighted some reports focused on allergic inflammation when similar aspects of type 2 immunity may be operational in the context of helminth infections.…”

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

“…As an alarmin, IL-33 proceeds to function to promote an early shift toward a type 2 immune response, protective in the context of helminth infection. Upon interaction with its ligands, especially those expressed by ILC2s and mast cells, activated cells respond by considerably enhancing production of type 2 cytokines IL-5 and IL-13 (Henry et al, 2017). While not its only target, IL-33 is known to interact especially well with those ILC2s (Gorbacheva and Mitkin, 2019).…”

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

“…Type 2 immunity activation can exhibit either pathogenic or host-protective activity, e.g., during allergic responses or helminthic infection, respectively. However, there is evidence indicating that type 2 associated cytokines and cells can also have important functions under steady-state conditions [ 8 ]. In fact, non-immune cells in the intestine express the receptor chains for the two key type 2 cytokines, that is, IL-4 and IL-13.…”