Your browser doesn't support javascript.
Influenza, but not SARS-CoV-2, infection induces a rapid interferon response that wanes with age and diminished tissue-resident memory CD8+ T cells.
Nguyen, Thi Ho; McAuley, Julie L; Kim, Youry; Zheng, Ming Zm; Gherardin, Nicholas A; Godfrey, Dale I; Purcell, Damian Fj; Sullivan, Lucy C; Westall, Glen P; Reading, Patrick C; Kedzierska, Katherine; Wakim, Linda M.
  • Nguyen TH; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • McAuley JL; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Kim Y; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Zheng MZ; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Gherardin NA; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Godfrey DI; Australian Research Council Centre of Excellence for Advanced Molecular Imaging University of Melbourne Melbourne VIC Australia.
  • Purcell DF; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Sullivan LC; Australian Research Council Centre of Excellence for Advanced Molecular Imaging University of Melbourne Melbourne VIC Australia.
  • Westall GP; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Reading PC; Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne VIC Australia.
  • Kedzierska K; Lung Transplant Service Alfred Hospital Melbourne VIC Australia.
  • Wakim LM; Lung Transplant Service Alfred Hospital Melbourne VIC Australia.
Clin Transl Immunology ; 10(1): e1242, 2021.
Article in English | MEDLINE | ID: covidwho-1064341
Semantic information from SemMedBD (by NLM)
1. Infectious Lung Disorder PROCESS_OF Older people
Subject
Infectious Lung Disorder
Predicate
PROCESS_OF
Object
Older people
2. Human tissue PART_OF Lung
Subject
Human tissue
Predicate
PART_OF
Object
Lung
3. Lung PART_OF Homo sapiens
Subject
Lung
Predicate
PART_OF
Object
Homo sapiens
4. Antiviral Response PRODUCES Interferon Type I
Subject
Antiviral Response
Predicate
PRODUCES
Object
Interferon Type I
5. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 DISRUPTS Memory T-Lymphocyte
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
DISRUPTS
Object
Memory T-Lymphocyte
6. Local LOCATION_OF Immune Cell
Subject
Local
Predicate
LOCATION_OF
Object
Immune Cell
7. Memory PROCESS_OF Persons
Subject
Memory
Predicate
PROCESS_OF
Object
Persons
8. Infectious Lung Disorder PROCESS_OF Older people
Subject
Infectious Lung Disorder
Predicate
PROCESS_OF
Object
Older people
9. Human tissue PART_OF Lung
Subject
Human tissue
Predicate
PART_OF
Object
Lung
10. Lung PART_OF Homo sapiens
Subject
Lung
Predicate
PART_OF
Object
Homo sapiens
11. Antiviral Response PRODUCES Interferon Type I
Subject
Antiviral Response
Predicate
PRODUCES
Object
Interferon Type I
12. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 DISRUPTS Memory T-Lymphocyte
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
DISRUPTS
Object
Memory T-Lymphocyte
13. Local LOCATION_OF Immune Cell
Subject
Local
Predicate
LOCATION_OF
Object
Immune Cell
14. Memory PROCESS_OF Persons
Subject
Memory
Predicate
PROCESS_OF
Object
Persons
ABSTRACT
Older individuals exhibit a diminished ability to respond to and clear respiratory pathogens and, as such, experience a higher rate of lung infections with a higher mortality rate. It is unclear why respiratory pathogens impact older people disproportionately. Using human lung tissue from donors aged 22-68 years, we assessed how the immune cell landscape in lungs changes throughout life and investigated how these immune cells respond following in vitro exposure to influenza virus and SARS-CoV-2, two clinically relevant respiratory viruses. While the frequency of most immune cell subsets profiled in the human lung remained stable with age, memory CD8+ T cells declined, with the tissue-resident memory (Trm) CD8+ T-cell subset being most susceptible to age-associated attrition. Infection of lung tissue with influenza virus resulted in an age-associated attenuation in the antiviral immune response, with aged donors producing less type I interferon (IFN), GM-CSF and IFNγ, the latter correlated with a reduction of IFNγ-producing memory CD8+ T cells. In contrast, irrespective of donor age, exposure of human lung cells to SARS-CoV-2, a pathogen for which all donors were immunologically naïve, did not trigger activation of local immune cells and did not result in the induction of an early IFN response. Our findings show that the attrition of tissue-bound pathogen-specific Trm in the lung that occurs with advanced age, or their absence in immunologically naïve individuals, results in a diminished early antiviral immune response which creates a window of opportunity for respiratory pathogens to gain a greater foothold.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article