Long-term surviving influenza infected cells evade CD8+ T cell mediated clearance

• DOI: 10.1371/journal.ppat.1008077
• Publication Date: 2019-09-27T00:35:25Z
• Authors: Jessica K. Fiege; Ian A. Stone; Rebekah E. Dumm; Barbara M. Waring; Brian T. Fife; Judith Agudo; Brian D. Brown; Nicholas S. Heaton; Ryan A. Langlois
• Keywords: Cytotoxicity, Immunologic; QH301-705.5; Cell Survival; Programmed Cell Death 1 Receptor; Mice, Transgenic; Adaptive Immunity; CD8-Positive T-Lymphocytes; B7-H1 Antigen; Mice; 03 medical and health sciences; 0302 clinical medicine; Influenza, Human; Animals; Humans; Biology (General); Lung; Cell Proliferation; Immune Evasion; Immunity, Cellular; RC581-607; 3. Good health; Mice, Inbred C57BL; Influenza A virus; Immunologic diseases. Allergy; Research Article

Influenza A virus (IAV) is a seasonal pathogen with the potential to cause devastating pandemics. IAV infects multiple epithelial cell subsets in respiratory tract, eliciting damage lungs. Clearance of primarily dependent on CD8+ T cells, which must balance control infection immunopathology. Using expressing Cre recombinase permanently label infected cells Cre-inducible reporter mouse, we previously discovered club that survive both lytic replication and cell-mediated clearance. In this study, demonstrate ciliated type I II alveolar can also become survivor cells. Survivor are stable lung long-term enhanced proliferation compared uninfected When investigated how evade killing observed upregulated inhibitory ligand PD-L1, but did not use PD-L1 killing. Instead our data suggest inherently resistant killing, instead no longer present antigen cannot be detected by Finally, evaluate failure kill these This work demonstrates additional types robustly proliferate long term. By sparing adaptive immune system may minimizing pathology associated infection.