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

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, 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.

Thi H. O. 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 Nüssing, Xiaoxiao Jia, Patrick Günther, Adam K. Wheatley, Stephen J. Kent, Malet Aban, Yi-Mo Deng, Karen L. Laurie, Aeron C. Hurt, Stephanie Gras, Jamie Rossjohn, Jane Crowe, Jianqing Xu, David Jackson, Lorena E. Brown, Nicole La Gruta, Weisan Chen, Peter C. Doherty, Stephen J. Turner, Tom C. Kotsimbos, Paul G. Thomas, Allen C. Cheng, Katherine Kedzierska