Innate lymphotoxin receptor mediated signaling promotes HSV-1 associated neuroinflammation and viral replication

Yong Liang, Kaiting Yang, Jingya Guo, Joanna Wroblewska, Yang Xin Fu, Hua Peng

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Abstract

Host anti-viral innate immunity plays important roles in the defense against HSV-1 infection. In this study, we find an unexpected role for innate LT/LIGHT signaling in promoting HSV-1 replication and virus induced inflammation in immunocompromised mice. Using a model of footpad HSV-1 infection in Rag1 -/- mice, we observed that blocking LT/LIGHT signaling with LTβR-Ig could significantly delay disease progression and extend the survival of infected mice. LTβR-Ig treatment reduced late proinflammatory cytokine release in the serum and nervous tissue, and inhibited chemokine expression and inflammatory cells infiltration in the dorsal root ganglia (DRG). Intriguingly, LTβR-Ig treatment restricted HSV-1 replication in the DRG but not the footpad. These findings demonstrate a critical role for LT/LIGHT signaling in modulating innate inflammation and promoting HSV-1 replication in the nervous system, and suggest a new target for treatment of virus-induced adverse immune response and control of severe HSV-1 infection.

Original languageEnglish (US)
Article number10406
JournalScientific Reports
Volume5
DOIs
StatePublished - May 20 2015

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