Severe COVID-19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils

被引：11

作者：

Leal, Vinicius N. C. ^{[1
]}

Andrade, Milena M. S. ^{[2
]}

Teixeira, Franciane M. E. ^{[2
]}

Cambui, Raylane A. G. ^{[1
]}

Roa, Mariela E. G. V. ^{[1
]}

Marra, Leticia G. ^{[1
]}

Yamada, Suemy M. ^{[1
]}

Alberca, Ricardo W. ^{[2
]}

Gozzi-Silva, Sarah C. ^{[2
]}

Yendo, Tatiana M. ^{[3
]}

Netto, Lucas C. ^{[4
]}

Duarte, Alberto J. S. ^{[2
]}

Sato, Maria N. ^{[2
]}

Pontillo, Alessandra ^{[1
,5
]}

机构：

[1] Univ Sao Paulo, Dept Imunol, Lab Imunogenet, Inst Ciencias Biomed, Sao Paulo, Brazil

[2] Hosp Clin Sao Paulo, Fac Med, Dept Dermatol, Lab Invest Med Dermatol & Imunodeficiencias LIM 56, Sao Paulo, Brazil

[3] Univ Sao Paulo, Fac Med, Dept Dermatol, Inst Med Trop, Sao Paulo, Brazil

[4] Hosp Clin Sao Paulo, Unidade Terapia Intens, FMUSP, Sao Paulo, Brazil

[5] Lineu Prestes, 1730 Cidade Univ, Sao Paulo, SP, Brazil

来源：

SCANDINAVIAN JOURNAL OF IMMUNOLOGY | 2023年 / 97卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

COVID-19; inflammasome; neutrophils; NLRP3; INTERLEUKIN-1-BETA SECRETION; ACTIVATION; EXPRESSION;

D O I：

10.1111/sji.13247

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

SARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1 beta and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.

引用

页数：13

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