LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation
Year: 2010
Type: article
Abstract: BACKGROUND: Infection with adeno-associated virus (AAV) vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. METHODS/PRINCIPAL FINDINGS: We showed that expressing LIGHT with an adenovirus vector (Ad) in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbetaR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbetaR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that LIGHT interaction with the LTbetaR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immuno-therapeutics in treating people chronically infected with hepato-tropic viruses.
Source: PLoS ONE
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1336697150, Enhanced Immunity Inside of Tumor Microenvironment, CO-FACILITATORS: NOVEL REGULATORS OF HORMONE METABOLISM, Treg in HIV-1 Replication and Pathogenesis, G4821723540, A Novel Humanized Mouse Model for Studying HIV/HCV Co-Infection and Liver Disease, Basic Immune Mechanisms, Pathogenesis of HCV in a Novel Mouse Model, G6655552579, G8362371087
OpenAlex ID: W2122590618