Upregulation of type 1 conventional dendritic cells implicates antigen cross-presentation in multisystem inflammatory syndrome

Autor: Robert Winchester, Alexis Boneparth, Mark Gorelik, Samantha B. Gaines, Peter S. Dayan, Mateo L. Amezcua, Janice J. Huang, Tamar R. Lubell, Marissa Dale, Mark D. Hicar
Rok vydání: 2022
Předmět:
Male
Sialic Acid Binding Ig-like Lectin 1
T-Lymphocytes
medicine.medical_treatment
CD38
Dendritic cells
Monocytes
Mean fluorescence intensity
MFI
Immunology and Allergy
Child
Antigens
Viral
CD64
Membrane Glycoproteins
Multisystem Inflammatory Syndrome in Children
MIS-C
Dendritic cells
DC
Systemic Inflammatory Response Syndrome
Up-Regulation
Killer Cells
Natural
Cytokine
medicine.anatomical_structure
Child
Preschool
Cytokines
Female
Macrophage activation syndrome
MAS
Uniform Manifold Approximation and Projection
UMAP
Adolescent
CLEC9A
NK cell cytotoxicity
Immunology
Human Leukocyte Antigen
HLA
Article
Immunophenotyping
Interferon-gamma
Cross-Priming
medicine
Humans
Kawasaki Disease (KD)
Kawasaki Disease
KD
Antigen-presenting cell
CD86
Antigen Cross Presentation
SARS-CoV-2
business.industry
Interleukins
Monocyte
Multisystem Inflammatory Syndrome in Children (MIS-C)
Models
Immunological
COVID-19
HLA-DR Antigens
Dendritic cell
medicine.disease
ADP-ribosyl Cyclase 1
Case-Control Studies
Macrophage activation syndrome
business
Zdroj: The Journal of Allergy and Clinical Immunology
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2021.10.015
Popis: Background Multisystem inflammatory syndrome in children (MIS-C) is an acute, febrile, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated syndrome, often with cardiohemodynamic dysfunction. Insight into mechanism of disease is still incomplete. Objective Our objective was to analyze immunologic features of MIS-C patients compared to febrile controls (FC). Methods MIS-C patients were defined by narrow criteria, including having evidence of cardiohemodynamic involvement and no macrophage activation syndrome. Samples were collected from 8 completely treatment-naive patients with MIS-C (SARS-CoV-2 serology positive), 3 patients with unclassified MIS-C–like disease (serology negative), 14 FC, and 5 MIS-C recovery (RCV). Three healthy controls (HCs) were used for comparisons of normal range. Using spectral flow cytometry, we assessed 36 parameters in antigen-presenting cells (APCs) and 29 in T cells. We used biaxial analysis and uniform manifold approximation and projection (UMAP). Results Significant elevations in cytokines including CXCL9, M-CSF, and IL-27 were found in MIS-C compared to FC. Classic monocytes and type 2 dendritic cells (DCs) were downregulated (decreased CD86, HLA-DR) versus HCs; however, type 1 DCs (CD11c+CD141+CLEC9A+) were highly activated in MIS-C patients versus FC, expressing higher levels of CD86, CD275, and atypical conventional DC markers such as CD64, CD115, and CX3CR1. CD169 and CD38 were upregulated in multiple monocyte subtypes. CD56dim/CD57−/KLRGhi/CD161+/CD38− natural killer (NK) cells were a unique subset in MIS-C versus FC without macrophage activation syndrome. Conclusion Orchestrated by complex cytokine signaling, type 1 DC activation and NK dysregulation are key features in the pathophysiology of MIS-C. NK cell findings may suggest a relationship with macrophage activation syndrome, while type 1 DC upregulation implies a role for antigen cross-presentation.
Databáze: OpenAIRE
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