Neutrophils Play an Essential Role in Cooperation with Antibody in both Protection against and Recovery from Pulmonary Infection with Influenza Virus in Mice

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Abstract
The role of polymorphonuclear leukocytes (PMN) in protection in the early phase and recovery in the late phase of influenza A virus infection was investigated by the depletion of PMN in, and passive transfer of anti-influenza virus antiserum to, mice with pulmonary infections. The depletion of PMN in normal mice by treatment with monoclonal antibody RB6-8C5 both increased the mortality rate and pulmonary virus titers from the early to the late phase after infection and delayed virus elimination in the late phase. The passive transfer of the antiserum to normal mice before or after infection abolished pulmonary virus propagation in the early phase, during 3 days, or rapidly decreased high virus titers in the plateau phase, on days 3 to 5, as well as accelerated virus elimination in the late phase, on day 7, after infection, respectively. The passive transfer of the antiserum to PMN-depleted mice could neither prevent the more rapid virus propagation in the early phase, diminish the higher virus titers in the plateau phase, nor accelerate the markedly delayed virus elimination in the late phase after infection in comparison to those for controls. The antibody responses to the virus began to increase on day 7 after infection in normal and PMN-depleted mice. The prevention of virus replication, cytotoxic activity in virus-infected cell cultures, and phagocytosis of the virus in vitro by PMN were all augmented in the presence of the antiserum. These results indicate that PMN play an essential role in virus elimination in both protection against and recovery from infection, in cooperation with the antibody response.