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

doi:10.1038/srep10406

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 language	English (US)
Article number	10406
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep10406
State	Published - May 20 2015

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title = "Innate lymphotoxin receptor mediated signaling promotes HSV-1 associated neuroinflammation and viral replication",

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.",

author = "Yong Liang and Kaiting Yang and Jingya Guo and Joanna Wroblewska and Fu, {Yang Xin} and Hua Peng",

note = "Funding Information: We are grateful to Fu laboratory, especially Dr. Xiaohuan Guo, for helpful suggestions and comments on the project. This work was supported by: National Nature and Science Foundation of China (No. 81471579) to H.P.; the National Basic Research Program 973 of China (No. 2012CB519002) and National Science and Technology Major Project of China (No. 2012ZX10001006) to H.P.",

year = "2015",

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doi = "10.1038/srep10406",

language = "English (US)",

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AU - Liang, Yong

AU - Yang, Kaiting

AU - Guo, Jingya

AU - Wroblewska, Joanna

AU - Fu, Yang Xin

AU - Peng, Hua

N1 - Funding Information: We are grateful to Fu laboratory, especially Dr. Xiaohuan Guo, for helpful suggestions and comments on the project. This work was supported by: National Nature and Science Foundation of China (No. 81471579) to H.P.; the National Basic Research Program 973 of China (No. 2012CB519002) and National Science and Technology Major Project of China (No. 2012ZX10001006) to H.P.

PY - 2015/5/20

Y1 - 2015/5/20

N2 - 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.

AB - 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.

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

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