An innate antiviral pathway acting before interferons at epithelial surfaces

Marie B Iversen; Line S Reinert; Martin K Thomsen; Ieva Bagdonaite; Ramya Nandakumar; Natalia Cheshenko; Thaneas Prabakaran; Sergey Y Vakhrushev; Malgosha Krzyzowska; Sine K Kratholm; Fernando Ruiz-Perez; Steen V Petersen; Stanislas Goriely; Bo Martin Bibby; Kristina Eriksson; Jürgen Ruland; Allan R Thomsen; Betsy C Herold; Hans H Wandall; Sebastian Frische; Christian K Holm; Søren R Paludan

doi:10.1038/ni.3319

An innate antiviral pathway acting before interferons at epithelial surfaces

Marie B Iversen, Line S Reinert, Martin K Thomsen, Ieva Bagdonaite, Ramya Nandakumar, Natalia Cheshenko, Thaneas Prabakaran, Sergey Y Vakhrushev, Malgosha Krzyzowska, Sine K Kratholm, Fernando Ruiz-Perez, Steen V Petersen, Stanislas Goriely, Bo Martin Bibby, Kristina Eriksson, Jürgen Ruland, Allan R Thomsen, Betsy C Herold, Hans H Wandall, Sebastian FrischeChristian K Holm, Søren R Paludan

Glycomics Program

34 Citations (Scopus)

Abstract

Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.

Original language	English
Journal	Nature Immunology
Volume	17
Issue number	2
Pages (from-to)	150-158
Number of pages	9
ISSN	1529-2908
DOIs	https://doi.org/10.1038/ni.3319
Publication status	Published - 1 Feb 2016

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Iversen, M. B., Reinert, L. S., Thomsen, M. K., Bagdonaite, I., Nandakumar, R., Cheshenko, N., Prabakaran, T., Vakhrushev, S. Y., Krzyzowska, M., Kratholm, S. K., Ruiz-Perez, F., Petersen, S. V., Goriely, S., Bibby, B. M., Eriksson, K., Ruland, J., Thomsen, A. R., Herold, B. C., Wandall, H. H., ... Paludan, S. R. (2016). An innate antiviral pathway acting before interferons at epithelial surfaces. Nature Immunology, 17(2), 150-158. https://doi.org/10.1038/ni.3319

Iversen, MB, Reinert, LS, Thomsen, MK, Bagdonaite, I, Nandakumar, R, Cheshenko, N, Prabakaran, T, Vakhrushev, SY, Krzyzowska, M, Kratholm, SK, Ruiz-Perez, F, Petersen, SV, Goriely, S, Bibby, BM, Eriksson, K, Ruland, J, Thomsen, AR, Herold, BC, Wandall, HH, Frische, S, Holm, CK & Paludan, SR 2016, 'An innate antiviral pathway acting before interferons at epithelial surfaces', Nature Immunology, vol. 17, no. 2, pp. 150-158. https://doi.org/10.1038/ni.3319

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abstract = "Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.",

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AU - Iversen, Marie B

AU - Reinert, Line S

AU - Thomsen, Martin K

AU - Bagdonaite, Ieva

AU - Nandakumar, Ramya

AU - Cheshenko, Natalia

AU - Prabakaran, Thaneas

AU - Vakhrushev, Sergey Y

AU - Krzyzowska, Malgosha

AU - Kratholm, Sine K

AU - Ruiz-Perez, Fernando

AU - Petersen, Steen V

AU - Goriely, Stanislas

AU - Bibby, Bo Martin

AU - Eriksson, Kristina

AU - Ruland, Jürgen

AU - Thomsen, Allan R

AU - Herold, Betsy C

AU - Wandall, Hans H

AU - Frische, Sebastian

AU - Holm, Christian K

AU - Paludan, Søren R

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AB - Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.

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An innate antiviral pathway acting before interferons at epithelial surfaces

Abstract

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