Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection
Elizabeth B. Wilson,1
Douglas H. Yamada,1
Bruce J. Aronow,3
Christopher L. Karp,4,*
David G. Brooks1,
Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN- production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.
1 Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. 2 Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. 3 Division of Biomedical Informatics and Division of Developmental Biology, Cincinnati Childrens Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. 4 Division of Molecular Immunology, Cincinnati Childrens Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
* Present address: The Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.
The editors suggest the following Related Resources on Science sites:
In Science Magazine
Pamela M. Odorizzi and E. John Wherry (12 April 2013) Science340 (6129), 155.
[DOI: 10.1126/science.1237568] |Summary »|Full Text »|PDF »
John R. Teijaro, Cherie Ng, Andrew M. Lee, Brian M. Sullivan, Kathleen C. F. Sheehan, Megan Welch, Robert D. Schreiber, Juan Carlos de la Torre, and Michael B. A. Oldstone (12 April 2013) Science340 (6129), 207.
[DOI: 10.1126/science.1235214] |Abstract »|Full Text »|PDF »|Supplementary Materials »
In Science Signaling
Kristen L. Mueller (16 April 2013) Sci. Signal.6 (271), ec88.
[DOI: 10.1126/scisignal.2004240] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pharmacological Inhibition of Type I Interferon Signaling Protects Mice Against Lethal Sepsis.
L. Dejager, S. Vandevyver, M. Ballegeer, E. Van Wonterghem, L.-L. An, J. Riggs, R. Kolbeck, and C. Libert (2013)
The Journal of Infectious Disease
|Abstract »|Full Text »|PDF »
Confounding roles for type I interferons during bacterial and viral pathogenesis.