Effects of a primary influenza infection on susceptibility to a secondary Streptococcus pneumoniae infection
McNamee, Lynnelle Ann.
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Influenza infections result in increased susceptibility to a secondary Streptococcus pneumoniae infection. The aim of the present studies was to determine the mechanism(s) responsible for this increase in susceptibility. Using an in vivo co-infection model, we found that susceptibility to S. pneumoniae was significantly increased at 6 days but not 3 days after an influenza infection. We depleted mice of neutrophils and found that neutrophils were important in the response to S. pneumoniae in mice infected with bacteria only or those infected with influenza for 3 days prior to a S. pneumoniae infection. However, at 6 days, neutrophil depletion did not alter the response to bacterial growth, indicating that neutrophil function was altered. We measured reactive oxygen species (ROS) generation and phagocytosis of S. pneumoniae by lung and bone marrow neutrophils isolated from mice infected with influenza for 3 or 6 days and compared these to neutrophils from either mice stimulated with LPS to induce neutrophil migration or from uninfected mice.We found that neutrophils from influenza-infected mice were not able to either phagocytose bacteria or produce ROS in response to incubation with S. pneumoniae as readily as those from uninfected mice. In addition, neutrophil-depleted mice infected with influenza for 6 days were more susceptible to S. pneumoniae infection than either uninfected depleted mice or depleted mice infected with influenza for 3 days. Lung cytokine levels, such as IL-10, were elevated in mice infected with influenza for 6 days followed by S. pneumoniae. These data indicate that influenza-induced changes in neutrophil-independent mechanisms increase susceptibility to a S. pneumoniae infection. We developed a novel ex vivo tracheal explant system to determine whether influenza-induced tissue damage increases adherence of S. pneumoniae. Using this system, we were able to model an influenza infection from the initial stages of infection to denudation and repair of the respiratory epithelium. We found that adherence was only increased at the initial stages of influenza infection. Increases in adherence may be due primarily to decreased mucociliary clearance. Together, these data indicate that an influenza infection increases susceptibility to a S. pneumoniae infection by altering both neutrophil-dependent and-independent mechanisms.