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

Autoři: Jessica K. Fiege aff001;  Ian A. Stone aff001;  Rebekah E. Dumm aff002;  Barbara M. Waring aff001;  Brian T. Fife aff003;  Judith Agudo aff004;  Brian D. Brown aff004;  Nicholas S. Heaton aff002;  Ryan A. Langlois aff001
Působiště autorů: University of Minnesota, Department of Microbiology and Immunology and the Center for Immunology, Minneapolis, Minnesota, United States of America aff001;  Duke University School of Medicine, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America aff002;  University of Minnesota, Department of Medicine and the Center for Immunology, Minneapolis, Minnesota, United States of America aff003;  Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York City, New York, United States of America aff004
Vyšlo v časopise: Long-term surviving influenza infected cells evade CD8+ T cell mediated clearance. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1008077
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008077


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

Klíčová slova:

Cell cycle and cell division – Cell staining – Cytotoxic T cells – Epithelial cells – Flow cytometry – Influenza A virus – T cells


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