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

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

Publication date: Sep 19, 2024

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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Concepts Keywords
Bacterial Adolescent
Exhausted Apoptosis
Immunophenotyping Bacterial Infections
Kawasaki Child
Viral Child, Preschool
COVID-19
Female
Fever
Humans
Infant
Interferons
Interferons
Male
Neutrophil Activation
Neutrophils
SARS-CoV-2
T-Lymphocytes

Semantics

Type Source Name
disease IDO cell
disease MESH syndromes
disease IDO host
disease MESH bacterial infection
disease MESH viral infection
disease MESH Kawasaki disease
pathway REACTOME Apoptosis
pathway REACTOME Interferon Signaling
disease MESH infections
disease MESH etiology
disease IDO pathogen
drug DRUGBANK Piroxicam
disease MESH toxic shock syndrome
disease MESH aneurysms
disease IDO production
disease MESH lymphopenia
disease MESH T cell exhaustion
disease MESH COVID 19
disease MESH pneumonitis
pathway REACTOME Signal Transduction
disease IDO blood
disease MESH convalescence
disease MESH encephalitis
disease MESH juvenile idiopathic arthritis
disease MESH macrophage activation syndrome
disease MESH reactive arthritis
disease MESH asthma
pathway KEGG Asthma
drug DRUGBANK Pidolic Acid
disease MESH Systemic Inflammatory Response Syndrome

Original Article

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