| First Author | Milora KA | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 5799 |
| PubMed ID | 28724920 | Mgi Jnum | J:253038 |
| Mgi Id | MGI:5926668 | Doi | 10.1038/s41598-017-05363-4 |
| Citation | Milora KA, et al. (2017) Interleukin-36beta provides protection against HSV-1 infection, but does not modulate initiation of adaptive immune responses. Sci Rep 7(1):5799 |
| abstractText | 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. |
