Role and mechanism of immunomodulation by Influenza virus and its components in the predisposition to bacterial disease during Influenza infection. (360G-Wellcome-086509_Z_08_Z)

There is overwhelming evidence to suggest that influenza infection predisposes individuals to, often more fatal, bacterial pneumonia however, the mechanisms that trigger susceptibility to bacterial disease during influenza infection are poorly understood. The increasing likelihood that highly pathogenic avian influenza viruses will cause the next worldwide pandemic underscores the need to understand the multiple mechanisms underlying the interaction between influenza virus and bacterial pathogen s.. We have demonstrated a novel pathway of immunosuppression associated with influenza haemagglutinin (HA) based on down regulation of LPS-induced bioactive IL12p70 production in vivo in a mouse model and in vitro by murine bone marrow derived dendritic cells (BMDCs). We have further evidence that live influenza infection also down regulates LPS induced IL-12p70 expression in human dendritic cells. IL-12p70 is a key cytokine which affords protection against bacterial infections which have been associated with complications of influenza infection such as streptococcus pneumonia. This study proposes to investigate the role of this immunomodulation by influenza virus and its component HA in the predisposition to pneumococcal infection in vivo and to investigate the molecular mechanisms underlying transcriptional changes in BMDCs in response to HA