Modulation of Anti-Viral and Anti-Bacterial B Cell Responses in Super-infections (105.36)

Abstract

Abstract Respiratory tract infections (RTIs) with influenza virus are a major global health concern, and together with secondary bacterial infections can cause fatal pneumonia. As B cells contribute to protection through the production of antibodies (Abs), we investigated how concomitant viral-bacterial super-infections alter the generation and maintenance of protective B cell responses in RTIs. We established two models of co-infections with influenza A virus (IAV) and Streptococcus pneumoniae (Sp). The first reflects individuals with a viral RTI that go on to contract a subsequent bacterial infection; the second considers individuals that are asymptomatic carriers of bacteria prior to contracting a viral RTI. Mice infected with Sp following IAV exhibit increased signs of morbidity, whereas mice carrying Sp prior to IAV exhibit less morbidity. Super-infection with Sp following -but not prior to- IAV significantly increases anti-viral serum Abs. Furthermore, the kinetics of the germinal center response and the ASC response in the lung-draining mediastinal lymph node and in the lungs are altered. We demonstrate that anti-viral Ab-specificities and -isotypes are differentially affected. Interestingly, the Ab response to Sp is not impacted in either scenario, suggesting distinct regulatory mechanisms for anti-viral and -bacterial B cell responses in these co-infection models.