Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children.
Humans
Child
Neutrophils
/ immunology
COVID-19
/ immunology
Male
Female
Child, Preschool
Systemic Inflammatory Response Syndrome
/ immunology
Fever
/ immunology
SARS-CoV-2
/ immunology
Infant
Interferons
/ metabolism
Bacterial Infections
/ immunology
T-Lymphocytes
/ immunology
Mucocutaneous Lymph Node Syndrome
/ immunology
Adolescent
Apoptosis
Neutrophil Activation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Sep 2024
19 Sep 2024
Historique:
received:
25
09
2023
accepted:
22
08
2024
medline:
20
9
2024
pubmed:
20
9
2024
entrez:
19
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39300098
doi: 10.1038/s41467-024-52246-0
pii: 10.1038/s41467-024-52246-0
doi:
Substances chimiques
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8224Subventions
Organisme : DH | National Institute for Health Research (NIHR)
ID : 2016-16-011
Organisme : DH | National Institute for Health Research (NIHR)
ID : ACL 2018
Organisme : DH | National Institute for Health Research (NIHR)
ID : 206508/Z/17/Z
Organisme : Wellcome Trust (Wellcome)
ID : 215214/Z/19/Z
Organisme : Wellcome Trust (Wellcome)
ID : MRF-160-0008-ELP-KAFO-C0801
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 848196, 668303, 279185
Investigateurs
Sarah van den Berg
(S)
Leire Estamiana Elorieta
(L)
Informations de copyright
© 2024. The Author(s).
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