Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

Interleukin (IL) -21 is produced by Natural Killer T (NKT) cells and CD4(+) T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK) cells and macrophages are also...

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Autores principales:	Sine K Kratholm, Marie B Iversen, Line Reinert, Simon K Jensen, Marianne Hokland, Thomas Andersen, Andrew Rankin, Deborah Young, Sebastian Frische, Søren R Paludan, Christian K Holm
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0756ae2766ab44d6aa95c929d0317a44
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spelling	oai:doaj.org-article:0756ae2766ab44d6aa95c929d0317a442021-11-18T08:41:53ZInterleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.1932-620310.1371/journal.pone.0081790https://doaj.org/article/0756ae2766ab44d6aa95c929d0317a442013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24358128/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Interleukin (IL) -21 is produced by Natural Killer T (NKT) cells and CD4(+) T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK) cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R) and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT) and IL-21R knock out (KO) mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2) infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i) WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i.) and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21) had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.Sine K KratholmMarie B IversenLine ReinertSimon K JensenMarianne HoklandThomas AndersenAndrew RankinDeborah YoungSebastian FrischeSøren R PaludanChristian K HolmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e81790 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sine K Kratholm Marie B Iversen Line Reinert Simon K Jensen Marianne Hokland Thomas Andersen Andrew Rankin Deborah Young Sebastian Frische Søren R Paludan Christian K Holm Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
description	Interleukin (IL) -21 is produced by Natural Killer T (NKT) cells and CD4(+) T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK) cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R) and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT) and IL-21R knock out (KO) mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2) infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i) WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i.) and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21) had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.
format	article
author	Sine K Kratholm Marie B Iversen Line Reinert Simon K Jensen Marianne Hokland Thomas Andersen Andrew Rankin Deborah Young Sebastian Frische Søren R Paludan Christian K Holm
author_facet	Sine K Kratholm Marie B Iversen Line Reinert Simon K Jensen Marianne Hokland Thomas Andersen Andrew Rankin Deborah Young Sebastian Frische Søren R Paludan Christian K Holm
author_sort	Sine K Kratholm
title	Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
title_short	Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
title_full	Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
title_fullStr	Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
title_full_unstemmed	Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.
title_sort	interleukin-21 receptor signalling is important for innate immune protection against hsv-2 infections.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0756ae2766ab44d6aa95c929d0317a44
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Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

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