Journal of immunology (Baltimore, Md. : 1950) · 2024
NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dick Jenna K, Sangala Jules A, Krishna Venkatramana D, Khaimraj Aaron, Hamel Lydia, Erickson Spencer M, Hicks Dustin, Soigner Yvette, Covill Laura E, Johnson Alexander K, Ehrhardt Michael J, Ernste Keenan, Brodin Petter, Koup Richard A, Khaitan Alka, Baehr Carly, Thielen Beth K, Henzler Christine M, Skipper Caleb, Miller Jeffrey S, Bryceson Yenan T, Wu Jianming, John Chandy C, Panoskaltsis-Mortari Angela, Orioles Alberto, Steiner Marie E, Cheeran Maxim C J, Pravetoni Marco, Hart Geoffrey T
Аннотация
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.