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Defining the balance between optimal immunity and immunopathology in influenza virus infection

Nature Reviews Immunology (2024)Cite this article

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Abstract

Influenza A viruses remain a global threat to human health, with continued pandemic potential. In this Review, we discuss our current understanding of the optimal immune responses that drive recovery from influenza virus infection, highlighting the fine balance between protective immune mechanisms and detrimental immunopathology. We describe the contribution of innate and adaptive immune cells, inflammatory modulators and antibodies to influenza virus-specific immunity, inflammation and immunopathology. We highlight recent human influenza virus challenge studies that advance our understanding of susceptibility to influenza and determinants of symptomatic disease. We also describe studies of influenza virus-specific immunity in high-risk groups following infection and vaccination that inform the design of future vaccines to promote optimal antiviral immunity, particularly in vulnerable populations. Finally, we draw on lessons from the COVID-19 pandemic to refocus our attention to the ever-changing, highly mutable influenza A virus, predicted to cause future global pandemics.

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Fig. 1: Innate and adaptive immune responses to influenza virus infection.
Fig. 2: Insights and opportunities from influenza virus controlled human infection model studies.
Fig. 3: Immune responses during influenza vaccination versus influenza virus infection.

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Acknowledgements

K.K. is a recipient of a National Health and Medical Research Council (NHMRC) L1 Fellowship (1173871). T.H.O.N. and L.C.R. are recipients of a NHMRC EL1 Fellowship (1194036, 2026357). K.K., T.H.O.N. and L.C.R. are supported by NHMRC MRFF Award (2016062). B.Y.C. is supported by NHMRC Ideas Grants (2001346 and 2019097). R.S.T. is supported by the National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre (BRC; NIHR Imperial BRC grant P70668), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England/UK Health Security Agency and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UH2AI176172. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Thi H. O. Nguyen, Louise C. Rowntree, Brendon Y. Chua & Katherine Kedzierska

  2. National Heart and Lung Institute, Imperial College London, London, UK

    Ryan S. Thwaites

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T.H.O.N., L.C.R. and B.Y.C. contributed equally to all aspects of the article. All authors contributed to all aspects of the article.

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Nguyen, T.H.O., Rowntree, L.C., Chua, B.Y. et al. Defining the balance between optimal immunity and immunopathology in influenza virus infection. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01029-1

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