Journal article

Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients

Thi HO Nguyen, Marios Koutsakos, Carolien E van de Sandt, Jeremy Chase Crawford, Liyen Loh, Sneha Sant, Ludivine Grzelak, Emma K Allen, Tim Brahm, E Bridie Clemens, Maria Auladell, Luca Hensen, Zhongfang Wang, Simone Nussing, Xiaoxiao Jia, Patrick Gunther, Adam K Wheatley, Stephen J Kent, Malet Aban, Yi-Mo Deng Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

Abstract

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels. Influenza disease correlates with increases in IL-6/IL-8/MIP-1α/β cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells correlates with peak antibody-secreting cells and influenza heamaglutinin-specific memory B-cell numbers..

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Grants

Awarded by The Australian National Health and Medical Research Council (NHMRC) NHMRC Program Grant


Awarded by NIAID UO1 grant


Awarded by NHMRC EL1 Fellowship


Awarded by European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant


Awarded by St. Jude Center of Excellence for Influenza Research and Surveillance (NIAID)


Awarded by NHMRC


Funding Acknowledgements

We thank Jill Garlick, Janine Roney, and the research nurses at the Alfred Hospital, Nicola Bird, Kim Harland, Louise Carolan and Bernadette McCudden for their technical assistance. Thank you to Professors David Fairlie and Jim McCluskey for the MR1-5'OP-RU tetramer. We also thank the study participants for providing blood for research purposes. This work was supported by The Australian National Health and Medical Research Council (NHMRC) NHMRC Program Grant (1071916) to K.K., S.J.T., N.L.G., A.K., D.C.J., L.E.B., W.C., and a NIAID UO1 grant 1U01AI144616-01 "Dissection of Influenza Vaccination and Infection for Childhood Immunity" (DIVINCI) to K.K. and P.G.T. THON is supported by the NHMRC EL1 Fellowship (#1194036). M.K., M.Au, L.H. and S.N. were recipients of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. C.E.S. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement No. 792532. E.B.C. is a NHMRC Peter Doherty Fellow. S.S. was a recipient Victoria India Doctoral Scholarship and Melbourne International Fee Remission Scholarship, University of Melbourne. The Melbourne WHO Collaborating Centre for Reference Research on Influenza is supported by the Australian Government Department of Health. S.G. is a NHMRC SRF-Level A Fellow. J.R. is supported by an ARC Laureate fellowship. N.L.G. is supported by a NHMRC Ideas grant, ARC Discovery Project and ARC Future Fellowship. P.G.T. is supported by the St. Jude Center of Excellence for Influenza Research and Surveillance (NIAID Contract HHSN27220140006C), R01 AI 107625, R01AI136514 and ALSAC. ACC is a NHMRC Career Development (level 2) Fellow. K.K. was supported by a NHMRC Senior Research Fellowship Level B (#1102792), NHMRC Investigator Grant (#1173871) and the University of Melbourne Dame Kate Campbell Fellowship.