IL-33-binding HpARI family homologues with divergent effects in suppressing or enhancing type 2 immune responses

TY - JOUR

T1 - IL-33-binding HpARI family homologues with divergent effects in suppressing or enhancing type 2 immune responses

AU - Colomb, Florent

AU - Ogunkanbi, Adefunke

AU - Jamwal, Abhishek

AU - Dong, Beverly

AU - Maizels, Rick M.

AU - Finney, Constance A. M.

AU - Wasmuth, James D.

AU - Higgins, Matthew K.

AU - McSorley, Henry J.

N1 - Publisher Copyright: Copyright © 2024 American Society for Microbiology. All Rights Reserved.

PY - 2024/3

Y1 - 2024/3

N2 - HpARI is an immunomodulatory protein secreted by the intestinal nematode Heligmosomoides polygyrus bakeri, which binds and blocks IL-33. Here, we find that the H. polygyrus bakeri genome contains three HpARI family members and that these have different effects on IL-33-dependent responses in vitro and in vivo, with HpARI1+2 suppressing and HpARI3 amplifying these responses. All HpARIs have sub-nanomolar affinity for mouse IL-33; however, HpARI3 does not block IL-33-ST2 interactions. Instead, HpARI3 stabilizes IL-33, increasing the half-life of the cytokine and amplifying responses to it in vivo. Together, these data show that H. polygyrus bakeri secretes a family of HpARI proteins with both overlapping and distinct functions, comprising a complex immunomodulatory arsenal of host-targeted proteins.

AB - HpARI is an immunomodulatory protein secreted by the intestinal nematode Heligmosomoides polygyrus bakeri, which binds and blocks IL-33. Here, we find that the H. polygyrus bakeri genome contains three HpARI family members and that these have different effects on IL-33-dependent responses in vitro and in vivo, with HpARI1+2 suppressing and HpARI3 amplifying these responses. All HpARIs have sub-nanomolar affinity for mouse IL-33; however, HpARI3 does not block IL-33-ST2 interactions. Instead, HpARI3 stabilizes IL-33, increasing the half-life of the cytokine and amplifying responses to it in vivo. Together, these data show that H. polygyrus bakeri secretes a family of HpARI proteins with both overlapping and distinct functions, comprising a complex immunomodulatory arsenal of host-targeted proteins.

KW - IL-33

KW - helminth

KW - immunomodulation

UR - https://www.biorxiv.org/content/10.1101/2023.10.09.561567v1

UR - https://www.scopus.com/pages/publications/85187375111

U2 - 10.1128/iai.00395-23

DO - 10.1128/iai.00395-23

M3 - Article

C2 - 38294241

SN - 0019-9567

VL - 92

JO - Infection and Immunity

JF - Infection and Immunity

IS - 3

M1 - e00395-23

ER -