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

Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection. Chetty, A., Darby, M. G, Vornewald, P. M, Martín-Alonso, M., Filz, A., Ritter, M., McSorley, H. J, Masson, L., Smith, K., Brombacher, F., O'Shea, M. K, Cunningham, A. F, Ryffel, B., Oudhoff, M. J, Dewals, B. G, Layland, L. E, & Horsnell, W. G C Cell Host & Microbe, 29(4):579–593, Elsevier, apr, 2021.

Paper doi abstract bibtex

SUMMARY 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.

@article{Chetty2021,
abstract = {SUMMARY 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.},
author = {Chetty, Alisha and Darby, Matthew G and Vornewald, Pia M and Mart{\'{i}}n-Alonso, Mara and Filz, Anna and Ritter, Manuel and McSorley, Henry J and Masson, Lindi and Smith, Katherine and Brombacher, Frank and O'Shea, Matthew K and Cunningham, Adam F and Ryffel, Bernhard and Oudhoff, Menno J and Dewals, Benjamin G and Layland, Laura E and Horsnell, William G C},
doi = {10.1016/j.chom.2021.02.004},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Chetty et al. - 2021 - Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative.pdf:pdf},
issn = {19313128},
journal = {Cell Host {\&} Microbe},
keywords = {HSV-2,IL-33,IL-5,Nippostrongylus brasiliensis,OA,eosinophils,epithelial ulceration,fund{\_}ack,helminths,original,systemic immunity,vagina},
mendeley-tags = {OA,fund{\_}ack,original},
month = {apr},
number = {4},
pages = {579--593},
pmid = {33857419},
publisher = {Elsevier},
title = {{Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1931312821000834},
volume = {29},
year = {2021}
}

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