Interleukin-36beta provides protection against HSV-1 infection, but does not modulate initiation of adaptive immune responses
UMass Chan Affiliations
Horae Gene Therapy CenterDocument Type
Journal ArticlePublication Date
2017-07-19
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Interleukin-36 (IL-36) represents three cytokines, IL-36alpha, IL-36beta and IL-36gamma, which bind to the same receptor, IL-1RL2; however, their physiological function(s) remain poorly understood. Here, the role of IL-36 in immunity against HSV-1 was examined using the flank skin infection mouse model. Expression analyses revealed increased levels of IL-36alpha and IL-36beta mRNA in infected skin, while constitutive IL-36gamma levels remained largely unchanged. In human keratinocytes, IL-36alpha mRNA was induced by HSV-1, while IL-1beta and TNFalpha increased all three IL-36 mRNAs. The dominant alternative splice variant of human IL-36beta mRNA was isoform 2, which is the ortholog of the known mouse IL-36beta mRNA. Mice deficient in IL-36beta, but not IL-36alpha or IL-36gamma, succumbed more frequently to HSV-1 infection than wild type mice. Furthermore, IL-36beta(-/-) mice developed larger zosteriform skin lesions along infected neurons. Levels of HSV-1 specific antibodies, CD8(+) cells and IFNgamma-producing CD4(+) cells were statistically equal in wild type and IL-36beta(-/-) mice, suggesting similar initiation of adaptive immunity in the two strains. This correlated with the time at which HSV-1 genome and mRNA levels in primary skin lesions started to decline in both wild type and IL-36beta(-/-) mice. Our data indicate that IL-36beta has previously unrecognized functions protective against HSV-1 infection.Source
Sci Rep. 2017 Jul 19;7(1):5799. doi: 10.1038/s41598-017-05363-4. Link to article on publisher's siteDOI
10.1038/s41598-017-05363-4Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40402PubMed ID
28724920Related Resources
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© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/s41598-017-05363-4
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Except where otherwise noted, this item's license is described as © The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.