Article (Scientific journals)
Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection.
Chetty, Alisha; Darby, Matthew G.; Vornewald, Pia M. et al.
2021In Cell Host and Microbe, 29 (4), p. 579-593.e5
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Keywords :
HSV-2; IL-33; IL-5; Nippostrongylus brasiliensis; eosinophils; epithelial ulceration; helminths; systemic immunity; vagina
Abstract :
[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
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  ;  Université de Liège - ULiège > Immunologie vétérinaire
Layland, Laura E.
Horsnell, William G. C.
More authors (7 more) Less
Language :
English
Title :
Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection.
Publication date :
2021
Journal title :
Cell Host and Microbe
ISSN :
1931-3128
eISSN :
1934-6069
Publisher :
Cell Press, Cambridge, United States - Massachusetts
Volume :
29
Issue :
4
Pages :
579-593.e5
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 16 April 2021

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