FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

被引:400
作者
Junqueira, Caroline [1 ,2 ,3 ]
Crespo, Angela [1 ,2 ]
Ranjbar, Shahin [1 ,4 ]
de Lacerda, Luna B. [1 ,2 ,3 ]
Lewandrowski, Mercedes [1 ,2 ]
Ingber, Jacob [1 ,2 ]
Parry, Blair [5 ]
Ravid, Sagi [1 ,2 ]
Clark, Sarah [6 ]
Schrimpf, Marie Rose [1 ,2 ]
Ho, Felicia [1 ,2 ]
Beakes, Caroline [5 ]
Margolin, Justin [5 ]
Russell, Nicole [5 ]
Kays, Kyle [5 ]
Boucau, Julie [7 ]
Das Adhikari, Upasana [7 ]
Vora, Setu M. [1 ,8 ]
Leger, Valerie [9 ]
Gehrke, Lee [6 ,9 ]
Henderson, Lauren A. [2 ,10 ]
Janssen, Erin [2 ,10 ]
Kwon, Douglas [7 ]
Sander, Chris [11 ,12 ]
Abraham, Jonathan [6 ]
Goldberg, Marcia B. [6 ,13 ]
Wu, Hao [1 ,2 ,9 ]
Mehta, Gautam [14 ,15 ]
Bell, Steven [16 ]
Goldfeld, Anne E. [1 ,4 ]
Filbin, Michael R. [5 ]
Lieberman, Judy [1 ,2 ]
机构
[1] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA
[3] Fundacao Oswardo Cruz, Inst Rene Rachou, Belo Horizonte, MG, Brazil
[4] Harvard Med Sch, Dept Med, Boston, MA 02115 USA
[5] Massachusetts Gen Hosp, Inst Patient Care, Emergency Med, Boston, MA 02114 USA
[6] Harvard Med Sch, Bravatnik Inst, Dept Microbiol, Boston, MA 02115 USA
[7] Harvard Med Sch, MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA USA
[8] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[9] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[10] Boston Childrens Hosp, Div Immunol, Boston, MA USA
[11] Harvard Med Sch, Dana Farber Canc Inst, cBio Ctr, Boston, MA 02115 USA
[12] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA
[13] Massachusetts Gen Hosp, Ctr Bacterial Pathogenesis, Dept Med, Div Infect Dis, Boston, MA 02114 USA
[14] UCL, Inst Liver & Digest Hlth, London, England
[15] Fdn Liver Res, Inst Hepator, London, England
[16] Univ Cambridge, Dept Clin Neurosci, Cambridge, England
基金
美国国家卫生研究院;
关键词
ANTIBODIES; LESSONS;
D O I
10.1038/s41586-022-04702-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
SARS-CoV-2 can cause acute respiratory distress and death in some patients(1). Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear(2). Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fc. receptors. The plasma of vaccine recipients does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.
引用
收藏
页码:576 / +
页数:17
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