Because of their important role in antigen presentation to T cells, we also assessed the ability of primary dendritic cells to productively replicate pandemic H1N1 and human H5N1 viruses ( Figure 6A To determine if innate immune cells are being productively infected in vivo, macrophages and dendritic cells were purified from lungs of infected mice and cultured for infectious virus. Lungs from infected (3 days p.i.) mice were harvested and ex vivo cultures containing either lung macrophages or dendritic cells were sampled for infectious virus over a 65 hour time period. While the seasonal influenza isolate, TX/91 virus was not produced from either macrophages (CD11b+) or dendritic (CD11c+) cells, the 1918 pandemic virus as well as the two human H5N1 isolates were released into the culture supernatant (Figure 7) , indicating that these cells are being productively infected in the mouse lung. In CD11b+ (macrophages) cell cultures ( Figure 7A Figure 7B ). These data further demonstrate that mouse lung macrophages and dendritic cells are susceptible to highly pathogenic influenza virus infection in the lung tissue.