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

Chetty, Alisha, Darby, Matthew G., Vornewald, Pia M., Martín-Alonso, Mara, Filz, Anna, Ritter, Manuel, McSorley, Henry J., Masson, Lindi, Smith, Katherine, Brombacher, Frank, O'Shea, Matthew K., Cunningham, Adam F., Ryffel, Bernhard, Oudhoff, Menno J., Dewals, Benjamin G., Layland, Laura E. and Horsnell, William G.C. 2021. Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection. Cell Host and Microbe 29 (4) , pp. 579-593. 10.1016/j.chom.2021.02.004

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 1931-3128
Date of First Compliant Deposit: 15 April 2021
Date of Acceptance: 8 February 2021
Last Modified: 16 Apr 2021 13:30
URI: https://orca.cardiff.ac.uk/id/eprint/140509

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