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.
authors.affiliation: 1] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 1] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Kaiting
authors.initials: K
authors.lastname: Yang
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wroblewska
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Peng
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation; D053259:Lymphotoxin beta Receptor / Q000737:chemistry / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism / Q000821:virology; D015996:Survival Rate; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D018925:Chemokines; D016207:Cytokines; D018398:Homeodomain Proteins; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C064658:RAG-1 protein