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Sci Rep. 2017 Jul 19;7(1):5799. doi: 10.1038/s41598-017-05363-4.

Interleukin-36β provides protection against HSV-1 infection, but does not modulate initiation of adaptive immune responses.

Author information

1
Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA.
2
Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
3
Schepens Eye Research Institute - MEEI, Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
ProMetic, Washington DC, USA.
6
Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA. liselott@temple.edu.
7
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. liselott@temple.edu.
8
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. liselott@temple.edu.

Abstract

Interleukin-36 (IL-36) represents three cytokines, IL-36α, IL-36β and IL-36γ, 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-36α and IL-36β mRNA in infected skin, while constitutive IL-36γ levels remained largely unchanged. In human keratinocytes, IL-36α mRNA was induced by HSV-1, while IL-1β and TNFα increased all three IL-36 mRNAs. The dominant alternative splice variant of human IL-36β mRNA was isoform 2, which is the ortholog of the known mouse IL-36β mRNA. Mice deficient in IL-36β, but not IL-36α or IL-36γ, succumbed more frequently to HSV-1 infection than wild type mice. Furthermore, IL-36β-/- mice developed larger zosteriform skin lesions along infected neurons. Levels of HSV-1 specific antibodies, CD8+ cells and IFNγ-producing CD4+ cells were statistically equal in wild type and IL-36β-/- 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-36β-/- mice. Our data indicate that IL-36β has previously unrecognized functions protective against HSV-1 infection.

PMID:
28724920
PMCID:
PMC5517484
DOI:
10.1038/s41598-017-05363-4
[Indexed for MEDLINE]
Free PMC Article

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