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

Florent Colomb, Adefunke Ogunkanbi, Abhishek Jamwal, Beverly Dong, Rick M. Maizels, Constance A. M. Finney, James D. Wasmuth, Matthew K. Higgins, Henry J. McSorley (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numbere00395-23
JournalInfection and Immunity
Volume92
Issue number3
Early online date31 Jan 2024
DOIs
Publication statusPublished - Mar 2024

Keywords

  • IL-33
  • helminth
  • immunomodulation

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