B cell deficiency induces cytotoxic effector memory CD8 T cells during influenza-associated bacterial pneumonia 3818

Abstract Description Influenza causes significant worldwide morbidity. Secondary bacterial pneumonia caused by methicillin resistant Staphylococcus aureus (MRSA) increases morbidity and mortality. Preceding influenza memory improves control of super-infection with MRSA. B cells protect against influenza infection via antibodies, but their impact on CD8 T cell function is unknown. Mice were inoculated with H3N2 influenza and 54 days later with H1N1 influenza to model heterosubtypic memory. Mice were super-infected with MRSA 6 days following H1N1 infection. Data from B cell deficient (µMT), attenuated influenza-specific antibody (MD4), and lacking secreted antibody (IgMi) mice showed that loss of influenza-specific antibody did not impact pathogen burden, but did significantly increase weight loss and lung injury. Loss of influenza-specific antibody increased recruitment of resident and effector memory cytotoxic CD8 T cells in the lung. Transcriptional and flow cytometric analysis showed that these CD8 T cells display ‘exhaustion-like’ and cytotoxic signatures. Depletion of cytotoxic CD8 T cells prior to MRSA challenge led to an increase in viral and bacterial burden only in B cell deficient mice, emphasizing the importance of antibody for heterotypic immunity. We propose that loss of influenza-specific antibody production leads to increased formation of cytotoxic memory CD8 T cells, which are important for pathogen clearance, but also contribute towards lung inflammation. Funding Sources UPMC Children’s Hospital Research Advisory Committee Award HL107380 Topic Categories Mucosal and Regional Immunology (MUC)