Abstract
ILCs burst onto the immunological scene with their involvement in bacterial and helminth infections. As their influence has emerged, it has become clear that they play a fundamental role in regulating barrier tissue homeostasis and the immune response during inflammation. A subset of ILCs, ILC2s, has become the focus of attention for many helminth biologists—stepping into the limelight as both the elusive initiator and amplifier of the type-2 response. In many of the early reports, conclusions as to their function were based on experiments using unadapted parasites or immune-compromised hosts. In this review we re-examine the generation and function of type-2 ILCs in helminth infection and the extent to which their roles may be essential or redundant, in both primary and challenge infections. ILC2s will be discussed in terms of a broader innate network, which when in dialogue with adaptive immunity, allows the generation of the anti-parasite response. Finally, we will review how helminths manipulate ILC2 populations to benefit their survival, as well as dampen systemic inflammation in the host, and how this understanding may be used to improve strategies to control disease.
Highlights
Parasitic helminth infections by tapeworms, roundworms or flukes present an ongoing threat to human health and quality of life, and significantly dampen agricultural productivity through infection of livestock
This study revealed adenosine as a novel danger-associated molecular pattern (DAMP), responsible for initiating helminth-induced type-2 responses, through activation of ILC2s
ILC2 activity was reported to be negatively regulated by acetylcholine through the nicotinic acetylcholine receptor α7nAChR [83], catecholamines ligating the β2-adrenergic receptor [84], as well as the aryl hydrocarbon receptor (AhR) in the latter case this may operate through preferential expansion of ILC3 cells [85]
Summary
Parasitic helminth infections by tapeworms, roundworms or flukes present an ongoing threat to human health and quality of life, and significantly dampen agricultural productivity through infection of livestock. Over 2 billion people are infected with helminth parasites [1], and in the absence of any vaccines, control relies on repeated drug treatment. Understanding immunity to helminths is essential to develop new vaccines to eliminate these infections. Until about a decade ago it was suggested that resistance to helminth infection relies predominantly on T helper 2 (Th2) cells of the adaptive immune system, orchestrating nematode expulsion in an antigen-specific manner. Soon re-branded as ILC2s, these innate cells were found localized to differing tissues and primed to act as first responders to the immune challenges such as helminth infections before adaptive immunity has developed [10]. Since the discovery of these innate Th2 cell surrogates, research delineating ILC2 functions, especially in the disease settings of helminth infection and allergic asthma, have dominated the scientific field of type-2 immunity. ILC2s are stimulated by helminths in the tissues, such as Litomosoides sigmodontis in the pleural cavity [13] and by the eggs of Schistosoma mansoni in the liver and lungs [14]
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