@article{ad395111992f4f3bb34f3f94f6309f1d,
title = "Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection",
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.",
keywords = "HSV-2, IL-33, IL-5, Nippostrongylus brasiliensis, eosinophils, epithelial ulceration, helminths, systemic immunity, vagina",
author = "Alisha Chetty and Darby, {Matthew G.} and Vornewald, {Pia M.} and Mara Mart{\'i}n-Alonso and Anna Filz and Manuel Ritter and McSorley, {Henry J.} and Lindi Masson and Katherine Smith and Frank Brombacher and O'Shea, {Matthew K.} and Cunningham, {Adam F.} and Bernhard Ryffel and Oudhoff, {Menno J.} and Dewals, {Benjamin G.} and Layland, {Laura E.} and Horsnell, {William G. C.}",
note = "This study was supported by German Research Foundation (DFG) within the “German-Africa Cooperation Projects in Infectiology” (grant LA 2746/2 ); CNRS of Orl{\'e}ans (France) and European funding in Region Centre-Val de Loire ( FEDER no 2016-00110366 BIO-TARGET and EX005756 BIO-TARGET II); and the Poliomyelitis Research Foundation (PRF; 17/08). A.C., W.G.C.H., L.E.L., A.F., M.R., and L.M. were supported by the DFG ; A.C. was supported by the National Research Foundation of South Africa (NRF, grant 120685 ). P.M.V., M.M.-A., and M.J.O. were supported by the Research Council of Norway (Centre of Excellence ( 223255/F50 ), and Young Research Talent ( 274760 ). B.G.D. is a senior research associate of the F.R.S.-FNRS, Belgium. This research was funded in part by the Wellcome Trust (grant: 203135/Z/16/Z ). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.",
year = "2021",
month = apr,
day = "14",
doi = "10.1016/j.chom.2021.02.004",
language = "English",
volume = "29",
pages = "579--593.e5",
journal = "Cell Host & Microbe",
issn = "1931-3128",
publisher = "Elsevier",
number = "4",
}