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A helminth-derived suppressor of ST2 blocks allergic responses.

Published version
Peer-reviewed

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Authors

Chauché, Caroline 
Jamwal, Abhishek 
Hinchy, Elizabeth C 
Heieis, Graham 

Abstract

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.

Description

Keywords

Helminth, IL-33, ST2, allergy, asthma, human, immunology, infectious disease, inflammation, microbiology, mouse, parasite, Alternaria, Animals, Antigens, Helminth, Asthma, Cell Line, Humans, Immunologic Factors, Interleukin-1 Receptor-Like 1 Protein, Interleukin-33, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nematospiroides dubius, Ovalbumin

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Longfonds | Accelerate (The AWWA project)
Medical Research Council (MR/S000593/1)