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LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation
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 modula...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871052/ https://www.ncbi.nlm.nih.gov/pubmed/20498840 http://dx.doi.org/10.1371/journal.pone.0010585 |
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author | Washburn, Michael L. Kovalev, Grigoriy I. Koroleva, Ekaterina Fu, Yang-Xin Su, Lishan |
author_facet | Washburn, Michael L. Kovalev, Grigoriy I. Koroleva, Ekaterina Fu, Yang-Xin Su, Lishan |
author_sort | Washburn, Michael L. |
collection | PubMed |
description | 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. LTβR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTβR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that LIGHT interaction with the LTβR 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. |
format | Text |
id | pubmed-2871052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28710522010-05-24 LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation Washburn, Michael L. Kovalev, Grigoriy I. Koroleva, Ekaterina Fu, Yang-Xin Su, Lishan PLoS One Research Article 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. LTβR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTβR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that LIGHT interaction with the LTβR 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. Public Library of Science 2010-05-14 /pmc/articles/PMC2871052/ /pubmed/20498840 http://dx.doi.org/10.1371/journal.pone.0010585 Text en Washburn et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Washburn, Michael L. Kovalev, Grigoriy I. Koroleva, Ekaterina Fu, Yang-Xin Su, Lishan LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title | LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title_full | LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title_fullStr | LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title_full_unstemmed | LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title_short | LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation |
title_sort | light induces distinct signals to clear an aav-expressed persistent antigen in the mouse liver and to induce liver inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871052/ https://www.ncbi.nlm.nih.gov/pubmed/20498840 http://dx.doi.org/10.1371/journal.pone.0010585 |
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