Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

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Publication Details

Journal
Nature Communications
Published
2024-09-19
DOI
https://doi.org/10.1038/s41467-024-52246-0
Citations
3
Primary Topic
Kawasaki Disease and Coronary Complications
Type
article
Field-Weighted Citation Impact
1.72

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article

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children

Heather Jackson, Cynthia Bishop, Dominic Habgood-Coote, Paul Wellman et al.
3 citations
Nature Communications
Kawasaki Disease and Coronary Complications
1.72
article

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children

Heather Jackson, Cynthia Bishop, Dominic Habgood-Coote, Paul Wellman, Manu Shankar‐Hari, Elizabeth Whittaker, A.R. Jennings, Richard J. Ellis, Padmanabhan Ramnarayan, Harsita Patel, Nedyalko Petrov, Filomena Spada, Myrsini Kaforou, Sarah van den Berg, Julia Kenny, Tisham De, Emma Timms, Pierre Tissières, Victoria Wright, Samuel J. Nichols, Giselle D’Souza, Michael J. Carter, Katrina Todd, Jethro Herberg, Francesca Davis, Sarah Darnell, Matthew Fish, Jonathan Cohen, Shane M. Tibby, Aubrey J. Cunnington, Thomas Sun, Sobia Mustafa, Michael H. Malim, Maggie Nyirendra, Michael Levin, Jessica L. Thomas, Leire Estamiana Elorieta, Manuela Terranova-Barberio, Oliver Powell
article en
3 citations

Abstract

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Nature CommunicationsVol. 15(1)
Guy's Hospital (GB), St Thomas' Hospital (GB), Queen Mary University of London (GB), King's College London (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Université Paris-Saclay (FR), Edinburgh Royal Infirmary (GB), Institut de Biologie Intégrative de la Cellule (FR), St Mary's Hospital (GB), Evelina London Children's Healthcare (GB), Centre for Inflammation Research (GB), King's College Hospital (GB), Lewisham and Greenwich NHS Trust (GB), Imperial College London (GB)
Wellcome, Wellcome Trust, National Institute for Health and Care Research, Imperial College London, King's College London, European Commission, Rosetrees Trust, Horizon 2020 Framework Programme, Medical Research Council, Guy's and St Thomas' NHS Foundation Trust, NIHR Imperial Biomedical Research Centre
Good health and well-being
Openalex Percentile: Top 15%
Kawasaki Disease and Coronary Complications
1.72
DOIOpen Access PDFOpenAlex
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