Landscape of coordinated immune responses to H1N1 challenge in humans

Influenza is a significant cause of morbidity and mortality worldwide. Here we show changes in the abundance and activation states of more than 50 immune cell subsets in 35 individuals over 11 time points during human A/California/2009 (H1N1) virus challenge monitored using mass cytometry along with...

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Bibliographic Details
Published in:The Journal of clinical investigation 2020-11, Vol.130 (11), p.5800-5816
Main Authors: Rahil, Zainab, Leylek, Rebecca, Schürch, Christian M, Chen, Han, Bjornson-Hooper, Zach, Christensen, Shannon R, Gherardini, Pier Federico, Bhate, Salil S, Spitzer, Matthew H, Fragiadakis, Gabriela K, Mukherjee, Nilanjan, Kim, Nelson, Jiang, Sizun, Yo, Jennifer, Gaudilliere, Brice, Affrime, Melton, Bock, Bonnie, Hensley, Scott E, Idoyaga, Juliana, Aghaeepour, Nima, Kim, Kenneth, Nolan, Garry P, McIlwain, David R
Format: Article
Language:English
Subjects:
Age
Antibodies
Biomedical research
CD38 antigen
Cytokines
Cytometry
Dendritic cells
Development and progression
Disease susceptibility
Epidemics
Fatalities
Female
Health aspects
Humans
Immune response
Immune system
Immunologic research
Infections
Influenza
Influenza A Virus, H1N1 Subtype - immunology
Influenza, Human - immunology
Killer Cells, Natural - immunology
Learning algorithms
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Machine learning
Male
Monocytes
Morbidity
Pandemics
Plasma
Risk factors
Serology
Swine flu
T-Lymphocytes - immunology
Vaccines
Volunteers
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Summary:Influenza is a significant cause of morbidity and mortality worldwide. Here we show changes in the abundance and activation states of more than 50 immune cell subsets in 35 individuals over 11 time points during human A/California/2009 (H1N1) virus challenge monitored using mass cytometry along with other clinical assessments. Peak change in monocyte, B cell, and T cell subset frequencies coincided with peak virus shedding, followed by marked activation of T and NK cells. Results led to the identification of CD38 as a critical regulator of plasmacytoid dendritic cell function in response to influenza virus. Machine learning using study-derived clinical parameters and single-cell data effectively classified and predicted susceptibility to infection. The coordinated immune cell dynamics defined in this study provide a framework for identifying novel correlates of protection in the evaluation of future influenza therapeutics.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI137265