Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae after viral pneumonia.
Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.
Duke Scholars
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Related Subject Headings
- Transforming Growth Factor beta
- SARS-CoV-2
- Pneumonia, Viral
- Pandemics
- Orthomyxoviridae Infections
- Orthomyxoviridae
- Mice, Inbred C57BL
- Lung
- Influenza, Human
- Immunologic Memory
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- Transforming Growth Factor beta
- SARS-CoV-2
- Pneumonia, Viral
- Pandemics
- Orthomyxoviridae Infections
- Orthomyxoviridae
- Mice, Inbred C57BL
- Lung
- Influenza, Human
- Immunologic Memory