NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children

Jenna K Dick, Jules A. Sangala, Venkatramana D. Krishna, Aaron J Khaimraj, Lydia Hamel, Spencer M. Erickson, Dustin M Hicks, Yvette Soigner, Laura E. Covill, Alexander K. Johnson, Michael J Ehrhardt, Keenan Ernste, Petter Brodin, Richard A. Koup, Alka Khaitan, Carly Baehr, Beth K Thielen, Christy Henzler, Caleb P Skipper, Jeffrey S MillerYenan T. Bryceson, Jianming Wu, Chandy C. John, Angela Panoskaltsis-Mortari, Alberto Orioles, Marie E Steiner, Maxim C.J. Cheeran, Marco Pravetoni, Geoffrey T Hart

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1452-1466
Number of pages15
JournalJournal of Immunology
Volume213
Issue number10
DOIs
StatePublished - Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 by The American Association of Immunologists, Inc.

PubMed: MeSH publication types

  • Journal Article

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