The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

Highly pathogenic avian influenza H5N1 epidemics are a significant public health hazard. Genetically engineered H5N1 viruses with mammalian transmission activity highlight the potential risk of a human influenza H5N1 pandemic. Understanding the underlying principles of the innate immune system in response to influenza H5N1 viruses will lead to improved prevention and control of these potentially deadly viruses. gamma delta T cells act as the first line of defense against microbial infection and help initiate adaptive immune responses during the early stages of viral infection. In this study, we investigated the molecular mechanisms of gamma delta T cells in response to influenza H5N1 viral infection. We found that recombinant hemagglutinin (rHA) derived from three different strains of influenza H5N1 viruses elicited the activation of gamma delta T cells cultured in peripheral blood mononuclear cells (PBMCs). Both the cell surface expression of CD69, an early activation marker on gamma delta T cells, and the production of interferon-gamma (IFN-gamma) were significantly increased. Notably, the rHA protein-induced gamma delta T-cell activation was not mediated by TCR gamma delta, NKG2D or pattern recognition receptors (PRRs) or NKp46 receptors. The interaction of rHA proteins with sialic acid receptors may play a critical role in gamma delta T-cell activation. Our data may provide insight into the mechanisms underlying gamma delta T-cell activation in response to infection with H5N1 viruses.