Blocking Constant Interferon Signaling Allows the Immune System to Clear Chronic Viral Infections

They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors. Interferons were named after their ability to "interfere" with viral replication within host cells. IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T-lymphocytes; and they increase the ability of uninfected host cells to resist new viral infection. Certain symptoms, such as aching muscles and fever, are related to the production of IFNs during infection. While Type I interferons (IFN-I) are critical for antiviral immunity, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections.

Investigators at the University of California, Los Angeles (USA) injected mice suffering from chronic viral infections with an antibody that temporarily blocked IFN-I activity.

They reported in the April 12, 2013, issue of the journal Science that the 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-gamma production.

“When cells confront viruses, they produce Type I interferons, which trigger the immune system’s protective defenses and sets off an alarm to notify surrounding cells,” said senior author Dr. David Brooks, assistant professor of microbiology, immunology, and molecular genetics at the University of California, Los Angeles. “Type-I interferon is like the guy in the watch tower yelling, "Red alert,” when the marauders try to raid the castle.”

“What we saw was entirely illogical,” said Dr. Brooks. “We had blocked something critical for infection control and expected the immune system to lose the fight against infection. Instead, the temporary break in IFN-I signaling improved the immune system’s ability to control infection. Our next task will be to figure out why and how to harness it for therapies to treat humans.”

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University of California, Los Angeles