We’ve discussed CD8+ CTL cells and the mechanism recognition and killing of targeted cells using FasL and perforin mediated apoptosis. This paper discusses how another apoptotic pathway, TRAIL, is important in influenza infection. TRAIL has been seen to select for tumor cells and is an important tool for immune surveillance. The immune system also relies on TRAIL to clear some viral infections. The author show that TRAIL is directly associated with increased levels of influenza virus clearance and by inhibiting TRAIL using a monoclonal antibody, longer durations of influenza infection persisted. Using mice that express TRAIL normally and TRAIL deficient mice, they were able to make some interesting observations related to influenza. TRAIL positive mice could clear flu virus significantly in 6 days where as TRAIL deficient mice had increased morbidity and increased flu viral loads. Target cells in pulmonary infection also show the receptor for TRAIL, DR5, indicating that TRAIL might be very important for controlling flu virus. Actually, influenza was shown to increase TRAIL on CD8+ T-cells and it’s DR5 receptors on infected cells. This is a very interesting mechanism we have developed to control a virus. Usually, we are talking about how a virus has out-evolved us. Influenza specific CD8+ T-cells were also shown to have TRAIL while non-influenza specific CD8+ T-cells did not. Regardless of TRAIL expression, FasL, perforin, IFN-g, degranulation and total T-cell levels did not change indicating the importance of TRAIL for clearance as well as protection from lethal doses of influenza which killed over 80% of non-TRAIL expressing mice.
Can TRAIL deficiencies or inhibited expression be cause of virulence in some influenza infections? Could this also be related to other persistent viral infections?
E. L. Brincks, A. Katewa, T. A. Kucaba, T. S. Griffith, and K. L. Legge
CD8 T cells utilize TRAIL to control influenza virus infection.
J. Immunol., Nov 2008; 181: 7428.
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