Influenza a virus and Streptococcus pneumonia coinfection potentially promotes bacterial colonization and enhances B lymphocyte depression and reduction

Abstract

Influenza has frequently been epidemic in recent years. However, the mechanisms of severe pneumonia with postinfluenza Streptococcus pneumoniae (SP) secondary infection have not been fully understood. In this study, we explored the mechanisms of pneumonia in postinfluenza A virus (IAV) infection via a mouse model. Mice were intranasally inoculated with SP three days after IAV inoculation. We then collected samples at three time points to dynamically observe the pathological progression. In IAV infection alone, lymphocyte infiltration and widened alveolar intervals were observed. In the blood, levels of the CD19+, CD19+CD21+ and CD19+CD79β+B lymphocyte subpopulations were reduced, and IFN-γ and IL-10 were elevated. Slight atrophy was seen in the spleen, which was due to splenic B lymphocyteinitiated apoptosis through the mitochondrial pathway. When SP infection occurred after IAV infection, the pulmonary inflammation was significantly aggravated; a fair number of lymphocytes and neutrophils infiltrated simultaneously with exfoliated bronchial epithelial cells, vascular endothelial cells, widened alveolar septum and hemorrhaging. Increasing edema fluid and bacteria accumulated in the alveolar cavity. Decreased CD19+, CD19+CD21+ and CD19+CD79β+B lymphocyte subpopulations and increased interferon gamma (IFN-γ) or interleukin 10 (IL-10) were more prominent compared to those with viral infection alone. Spleen atrophy resulting from coinfection was more obvious because of massive splenic B lymphocyte apoptosis through the mitochondrial pathway compared to viral infection alone. This study shows that although inflammation caused by SP infection alone was temporary, preceding IAV infection provided favorable conditions for SP colonization and multiplication by destroying lung structure and suppressing humoral immunity. Synergistic IAV-SP coinfection is likely to facilitate more SP colonization and promote B lymphocyte-suppression and reduction. Eventually, the pneumonia worsened.

Keywords: B lymphocyte; Streptococcus pneumoniae; influenza A virus; pneumonia.