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

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

SUBMITTER: Milora KA 

PROVIDER: S-EPMC5517484 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature