SUSCEPTIBILITY OF MONONUCLEAR PHAGOCYTES TO INFLUENZA-A VIRUS-INFECTION AND POSSIBLE ROLE IN THE ANTIVIRAL RESPONSE

Among leukocytes, only monocytes and macrophages were found to be high ly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted aft er 4-6 h. Most macrophages died by apoptosis within 25-30 h. Before ce ll death, however, macrophages responded to influenza A virus with a h igh cytokine gene transcription and subsequent release of tumor necros is factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, interferon (I FN)-alpha/beta, and CC-chemokines. The basic mechanisms of virus-induc ed cytokine expression are still unknown and appear to involve transcr iption factors such as nuclear factor-kappa B and AP-1 which, however, were only activated for 2 h and declined below control values thereaf ter. After influenza A virus infection, only the mononuclear cell attr acting CC-chemokines macrophage inflammatory protein 1 alpha (MIP-1 al pha), MIP-1 beta, and RANTES were produced while the prototype neutrop hil CXC-chemoattractants IL-8 and GRO-alpha were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.