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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 ORCID: https://orcid.org/0000-0001-8150-5702, 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: 09 Nov 2022 10:44
URI: https://orca.cardiff.ac.uk/id/eprint/140509

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