Abstract
In contrast to the detrimental outcomes most often associated with the resolution of coinfections, the model presented here involving a localized Pneumocystis infection of the lung, followed 2 wk later by an influenza virus infection, results in a significant beneficial outcome for the host. In the week following the influenza infection, immunocompetent coinfected animals exhibited an accelerated rate of virus clearance, an accelerated appearance of higher influenza-specific neutralizing Ab titers in their serum and bronchoalveolar lavage fluid (BALF), significantly reduced inflammatory cytokine levels in their BALF, and reduced levels of morbidity relative to animals infected only with influenza virus. The beneficial outcome observed in coinfected immunocompetent animals was dependent on the ongoing resolution of a viable Pneumocystis infection. No differences in viral clearance were detected between coinfected and influenza-only-infected muMT mice or likewise for SCID mice. The accelerated anti-influenza response did not appear to be associated with influenza-specific CD8 T cell-mediated responses or NK cell responses in the lung. Rather, the increased rate of viral clearance was due to the enhancement of the influenza-specific Ab response, which in turn was transiently dependent upon the resolution of the ongoing Pneumocystis infection.