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

Autor: Fiege JK; University of Minnesota, Department of Microbiology and Immunology and the Center for Immunology, Minneapolis, Minnesota, United States of America., Stone IA; University of Minnesota, Department of Microbiology and Immunology and the Center for Immunology, Minneapolis, Minnesota, United States of America., Dumm RE; Duke University School of Medicine, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America., Waring BM; University of Minnesota, Department of Microbiology and Immunology and the Center for Immunology, Minneapolis, Minnesota, United States of America., Fife BT; University of Minnesota, Department of Medicine and the Center for Immunology, Minneapolis, Minnesota, United States of America., Agudo J; Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York City, New York, United States of America., Brown BD; Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York City, New York, United States of America., Heaton NS; Duke University School of Medicine, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America., Langlois RA; University of Minnesota, Department of Microbiology and Immunology and the Center for Immunology, Minneapolis, Minnesota, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2019 Sep 26; Vol. 15 (9), pp. e1008077. Date of Electronic Publication: 2019 Sep 26 (Print Publication: 2019).
DOI: 10.1371/journal.ppat.1008077
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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