Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection

Research output: Contribution to journalArticlepeer-review

Authors

  • Alisha Chetty
  • Matthew G Darby
  • Pia M Vornewald
  • Mara Martín-Alonso
  • Anna Filz
  • Manuel Ritter
  • Henry J McSorley
  • Lindi Masson
  • Katherine Smith
  • Frank Brombacher
  • Bernhard Ryffel
  • Menno J Oudhoff
  • Benjamin G Dewals
  • Laura E Layland

External organisations

  • Norwegian University of Science and Technology
  • University Hospital Bonn (UKB)
  • University of Dundee
  • Monash University
  • University of Cape Town
  • Cardiff University
  • CNRS-University of Orleans
  • Université de Liège
  • German Centre for Infection Research (DZIF), Bonn - Köln

Abstract

How helminths influence the pathogenesis of sexually transmitted viral infections is not comprehensively understood. Here, we show that an acute helminth infection (Nippostrongylus brasiliensis [Nb]) induced a type 2 immune profile in the female genital tract (FGT). This leads to heightened epithelial ulceration and pathology in subsequent herpes simplex virus (HSV)-2 infection. This was IL-5-dependent but IL-4 receptor alpha (Il4ra) independent, associated with increased FGT eosinophils, raised vaginal IL-33, and enhanced epithelial necrosis. Vaginal eosinophil accumulation was promoted by IL-33 induction following targeted vaginal epithelium damage from a papain challenge. Inhibition of IL-33 protected against Nb-exacerbated HSV-2 pathology. Eosinophil depletion reduced IL-33 release and HSV-2 ulceration in Nb-infected mice. These findings demonstrate that Nb-initiated FGT eosinophil recruitment promotes an eosinophil, IL-33, and IL-5 inflammatory circuit that enhances vaginal epithelial necrosis and pathology following HSV-2 infection. These findings identify a mechanistic framework as to how helminth infections can exacerbate viral-induced vaginal pathology.

Details

Original languageEnglish
Pages (from-to)579-593.e5
JournalCell Host & Microbe
Volume29
Issue number4
Early online date12 Mar 2021
Publication statusPublished - 14 Apr 2021