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J Clin Invest . Landscape of coordinated immune responses to H1N1 challenge in humans

tetano

Editor, Senior Moderator
J Clin Invest


. 2020 Oct 12;137265.
doi: 10.1172/JCI137265. Online ahead of print.
Landscape of coordinated immune responses to H1N1 challenge in humans


Zainab Rahil[SUP] 1 2 [/SUP], Rebecca Leylek[SUP] 2 [/SUP], Christian M Sch?rch[SUP] 1 2 [/SUP], Han Chen[SUP] 1 2 [/SUP], Zach Bjornson-Hooper[SUP] 1 2 [/SUP], Shannon R Christensen[SUP] 3 [/SUP], Pier Federico Gherardini[SUP] 4 [/SUP], Salil S Bhate[SUP] 1 2 5 [/SUP], Matthew H Spitzer[SUP] 5 [/SUP], Gabriela K Fragiadakis[SUP] 6 [/SUP], Nilanjan Mukherjee[SUP] 1 2 [/SUP], Nelson Kim[SUP] 1 2 [/SUP], Sizun Jiang[SUP] 1 2 [/SUP], Jennifer Yo[SUP] 7 [/SUP], Brice Gaudilliere[SUP] 8 [/SUP], Melton Affrime[SUP] 9 [/SUP], Bonnie Bock[SUP] 9 [/SUP], Scott E Hensley[SUP] 3 [/SUP], Juliana Idoyaga[SUP] 2 [/SUP], Nima Aghaeepour[SUP] 8 [/SUP], Kenneth Kim[SUP] 7 [/SUP], Garry P Nolan[SUP] 1 2 [/SUP], David R McIlwain[SUP] 1 2 9 [/SUP]



Affiliations

Abstract

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.

Keywords: Adaptive immunity; Immunology; Infectious disease; Influenza; Innate immunity.
 
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