Parasite induced IFN-γ treats severe H5N1 influenza infection (49.11)

Abstract

Abstract Outbreaks of influenza A viruses are a continued burden to society in terms of both human health and economic costs. Given the continuous evolution of the virus away from our limited antiviral therapies, new treatments are desperately needed. An alternative approach is through the identification of immune enhancement treatments. We show that mice chronically infected with the immune modulating protistian parasite Toxoplasma gondii survive lethal influenza infection. Because a non-infectious fraction of parasite extract elicits an immunologic response similar to live parasites, it was tested as a post-infection treatment for severe influenza virus. Extract administration two days post- lethal influenza infection enhanced survival, lowered viral titers, and reduced clinical disease. Examination of treated, influenza virus infected mice lacking lymphocytes showed that while the adaptive immune response is not absolutely required for enhanced survival, it is necessary for extract-mediated viral clearance. Mechanistic analysis of the extract induced-innate immune responses showed that interferon gamma (IFNγ) production is both necessary and sufficient for survival. These studies demonstrate that T. gondii may have beneficial properties for its warm-blooded host and a non-infectious component from one microbe can be used to enhance the immune response to a second microbe.