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

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Abstract / Description of output

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.
Original languageEnglish
Article number8224
Pages (from-to)8224
JournalNature Communications
Volume15
Issue number1
Early online date19 Sept 2024
DOIs
Publication statusPublished - 19 Sept 2024

Keywords / Materials (for Non-textual outputs)

  • Adolescent
  • Apoptosis
  • Bacterial Infections/immunology
  • COVID-19/immunology
  • Child
  • Child, Preschool
  • Female
  • Fever/immunology
  • Humans
  • Infant
  • Interferons/metabolism
  • Male
  • Mucocutaneous Lymph Node Syndrome/immunology
  • Neutrophil Activation
  • Neutrophils/immunology
  • SARS-CoV-2/immunology
  • Systemic Inflammatory Response Syndrome/immunology
  • T-Lymphocytes/immunology

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