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Landscape of coordinated immune responses to H1N1 challenge in humans

by Bhate, Salil S. , McIlwain, David R. , Schürch, Christian M. , Jiang, Sizun , Leylek, Rebecca , Mukherjee, Nilanjan , Aghaeepour, Nima , Gaudilliere, Brice , Gherardini, Pier Federico , Nolan, Garry P. , Kim, Kenneth , Spitzer, Matthew H. , Idoyaga, Juliana , Bock, Bonnie , Fragiadakis, Gabriela K. , Yo, Jennifer , Hensley, Scott E. , Chen, Han , Kim, Nelson , Affrime, Melton , Rahil, Zainab , Christensen, Shannon R. , Bjornson-Hooper, Zach

in 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

2020

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2020

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2020

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Journal Article

Landscape of coordinated immune responses to H1N1 challenge in humans

Bhate, Salil S.,

McIlwain, David R.,

Schürch, Christian M.,

Jiang, Sizun,

Leylek, Rebecca,

Mukherjee, Nilanjan,

Aghaeepour, Nima,

Gaudilliere, Brice,

Gherardini, Pier Federico,

Nolan, Garry P.,

Kim, Kenneth,

Spitzer, Matthew H.,

Idoyaga, Juliana,

Bock, Bonnie,

Fragiadakis, Gabriela K.,

Yo, Jennifer,

Hensley, Scott E.,

Chen, Han,

Kim, Nelson,

Affrime, Melton,

Rahil, Zainab,

Christensen, Shannon R.,

Bjornson-Hooper, Zach

2020

Overview

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.

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Publisher

American Society for Clinical Investigation

Subject

Age

/ Antibodies

/ Biomedical research