Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy.
Helminth parasites such as the nematode Heligmosomoides polygyrus strongly inhibit T helper type 2 (Th2) allergy, as well as colitis and autoimmunity. Here, we show that the soluble excretory/secretory products of H. polygyrus (HES) potently suppress inflammation induced by allergens from the common fungus Alternaria alternata. Alternaria extract, when administered to mice intranasally with ovalbumin (OVA) protein, induces a rapid (1-48 h) innate response while also priming an OVA-specific Th2 response that can be evoked 14 days later by intranasal administration of OVA alone. In this model, HES coadministration with Alternaria/OVA suppressed early IL-33 release, innate lymphoid cell (ILC) production of IL-4, IL-5, and IL-13, and localized eosinophilia. Upon OVA challenge, type 2 ILC (ILC2)/Th2 cytokine production and eosinophilia were diminished in HES-treated mice. HES administration 6 h before Alternaria blocked the allergic response, and its suppressive activity was abolished by heat treatment. Administration of recombinant IL-33 at sensitization with Alternaria/OVA/HES abrogated HES suppression of OVA-specific responses at challenge, indicating that suppression of early Alternaria-induced IL-33 release could be central to the anti-allergic effects of HES. Thus, this helminth parasite targets IL-33 production as part of its armory of suppressive effects, forestalling the development of the type 2 immune response to infection and allergic sensitization.
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
H J
HJ
McSorley
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
N F
NF
Blair
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
K A
KA
Smith
MRC Laboratory of Molecular Biology, Cambridge, UK.
A N J
AN
McKenzie
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
R M
RM
Maizels
D000485:Allergens / Q000494:pharmacology; D000528:Alternaria / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000947:Antigens, Helminth / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation; D000067596:Interleukin-33; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D000947:Antigens, Helminth; C506535:Il33 protein, mouse; D000067596:Interleukin-33