Jenna K Dick, Jules A Sangala, Venkatramana D Krishna, Aaron Khaimraj, Lydia Hamel, Spencer M Erickson, Dustin 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, Christine M Henzler, Caleb Skipper, Jeffrey S Miller, Yenan T Bryceson, Jianming Wu, Chandy C John, Angela Panoskaltsis-Mortari, Alberto Orioles, Marie E Steiner, Maxim C J Cheeran, Marco Pravetoni, Geoffrey T Hart
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引用次数: 0
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.
期刊介绍:
The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)