J Virol. 2011 Jul 6. [Epub ahead of print]
Parasite-Mediated Upregulation of NK Cell-Derived IFN{gamma} Protects Against Severe HPAI H5N1 Influenza Virus Infection.
O'Brien KB, Schultz-Cherry S, Knoll LJ.
SourceDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105;
Abstract
Outbreaks of influenza A viruses are associated with significant human morbidity worldwide. Given the increasing resistance to the available influenza drugs, new therapies for the treatment of influenza virus infection are needed. An alternative approach is to identify products that enhance a protective immune response. In these studies we demonstrate that infecting mice with the Th1-inducing parasite Toxoplasma gondii prior to highly pathogenic avian H5N1 influenza virus infection led to decreased lung viral titers and enhanced survival. A non-infectious fraction of T. gondii soluble antigens (STAg) elicits an immune response similar to live parasites and administration of STAg two days post-H5N1 influenza virus infection enhanced survival, lowered viral titers, and reduced clinical disease. STAg administration protected H5N1 virus infected mice lacking lymphocytes suggesting that while the adaptive immune response was not required for enhanced survival, it was necessary for STAg-mediated viral clearance. Mechanistically, we found that administration of STAg led to increased production of interferon gamma (IFNγ) from Natural Killer (NK) cells, which were both necessary and sufficient for survival. Further, administration of exogenous IFNγ alone enhanced survival from H5N1 influenza virus infection; although not to the same level as STAg treatment. These studies demonstrate that a non-infectious T. gondii extract enhances the protective immune response against severe H5N1 influenza virus infections even when a single dose is administered two days post-infection.
PMID:21734055[PubMed - as supplied by publisher]
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