Streptococcus pneumoniaecoinfection results in increased disease in a murine model of influenza B virus infection

Abstract

Abstract Secondary Streptococcus pneumoniae (Spn) infection is commonly associated with increased hospitalization and death following seasonal influenza virus infection. The animal models of influenza A virus (IAV) and secondary Spn coinfection have described the increased morbidity and mortality leading to several proposed mechanisms of enhanced disease. Influenza B virus (IBV) causes 25% of seasonal influenza cases and is associated with bacterial coinfection, yet little is known about the immune response to IBV and Spn coinfection. Here, we established a mouse model of IBV and Spn coinfection to study disease in singly and coinfected animals and define mechanism(s) of enhanced disease. Like IAV and Spn coinfection, infection with IBV followed by Spn inoculation resulted in increased morbidity and mortality compared to IBV or Spn infection alone. In IBV primed mice, Spn titers were increased early following bacterial inoculation and Spn rapidly migrated to the lung. Analysis of cytokines in the lung showed increased pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) responses with secondary Spn infection, which may be associated with enhanced disease. These data suggest that IBV infection initiates innate immune responses that are rapidly enhanced with Spn infection, leading to worsening disease. Ongoing studies include analysis of infiltrating cells during coinfection and histopathologic analysis to complement the innate response data to define mediators of clinical disease. NIH CIDER Contract #75N93021C00018