NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.

NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.

Publication date: Oct 11, 2024

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.

Concepts Keywords
Myeloid Cellular
Phagocytosis Cov
Postinfection Cytokine
Viral Dysfunction
Vivo Immune
Inflammatory
Mediated
Mis
Monocyte
Multisystem
Production
Sars
Syndrome
Testing

Semantics

Type Source Name
disease IDO cell
disease MESH Multisystem Inflammatory Syndrome in Children
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease MESH inflammation
disease IDO immune response
disease IDO production
disease IDO nucleic acid

Original Article

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