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

Author:

Nguyen Thi H. O.ORCID,Koutsakos Marios,van de Sandt Carolien E.ORCID,Crawford Jeremy ChaseORCID,Loh LiyenORCID,Sant Sneha,Grzelak Ludivine,Allen Emma K.,Brahm TimORCID,Clemens E. Bridie,Auladell MariaORCID,Hensen LucaORCID,Wang Zhongfang,Nüssing Simone,Jia Xiaoxiao,Günther PatrickORCID,Wheatley Adam K.ORCID,Kent Stephen J.ORCID,Aban Malet,Deng Yi-Mo,Laurie Karen L.,Hurt Aeron C.,Gras Stephanie,Rossjohn JamieORCID,Crowe Jane,Xu JianqingORCID,Jackson DavidORCID,Brown Lorena E.,La Gruta NicoleORCID,Chen WeisanORCID,Doherty Peter C.ORCID,Turner Stephen J.ORCID,Kotsimbos Tom C.,Thomas Paul G.ORCID,Cheng Allen C.,Kedzierska KatherineORCID

Abstract

AbstractHow 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, which phenotypically differs from vaccination-induced B-cell responses. Numbers of influenza-specific CD8+ or CD4+ T cells increase early in disease and retain an activated phenotype during patient recovery. We report the characterisation of immune cellular networks underlying recovery from influenza infection which are highly relevant to other infectious diseases.

Funder

Department of Health | National Health and Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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