Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019

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Metzemaekers, Mieke ^[1] ; Cambier, Seppe ^[1] ; Blanter, Marfa ^[1] ; Vandooren, Jennifer ^[2] ; de Carvalho, Ana Carolina ^{[1, 3, 4]} ; Malengier-Devlies, Bert ^[2] ; Vanderbeke, Lore ^[5] ; Jacobs, Cato ^[6] ; Coenen, Sofie ^[7] ; Martens, Erik ^[2] ; Portner, Noemie ^[1] ; Vanbrabant, Lotte ^[1] ; Van Mol, Pierre ^[8] ; Van Herck, Yannick ^[9] ; Van Aerde, Nathalie ^[10] ; Hermans, Greet ^[10] ; Gunst, Jan ^[10] ; Borin, Alexandre ^[3] ; Pereira, Bruna Toledo N. ^[4] ; Gomes, Arilson Bernardo dos S. P. ^[4] ; Muraro, Stefanie Primon ^[11] ; de Souza, Gabriela Fabiano ^[11] ; Farias, Alessandro S. ^[12] ; Proenca-Modena, Jose Luiz ^{[12, 11]} ; Vinolo, Marco Aurelio R. ^{[4, 12]} ; Consortium, Contagious ; Marques, Pedro Elias ^[1] ; Wouters, Carine ^{[2, 13, 14]} ; Wauters, Els ^[15] ; Struyf, Sofie ^[1] ; Matthys, Patrick ^[2] ; Opdenakker, Ghislain ^[2] ; Marques, Rafael Elias ^[3] ; Wauters, Joost ^[6] ; Gouwy, Mieke ^[1] ; Proost, Paul ^[1]

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^[1] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Lab Mol Immunol, Rega Inst, Leuven - Belgium

^[2] Katholieke Univ Leuven, Rega Inst, Lab Immunobiol, Dept Microbiol Immunol & Transplantat, Leuven - Belgium

^[3] Brazilian Biosci Natl Lab, LNBio, Brazilian Ctr Res Energy & Mat CNPEM, Campinas - Brazil

^[4] Univ Campinas UNICAMP, Inst Biol, Lab Immunoinflammat, Dept Genet Microbiol & Immunol, Campinas - Brazil

^[5] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Lab Clin Bacteriol & Mycol, Leuven - Belgium

^[6] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Lab Clin Infect & Inflammatory Disorders, Leuven - Belgium

^[7] Univ Hosp Leuven, Div Pediat, Leuven - Belgium

^[8] VIB KU Leuven, Dept Human Genet, Lab Translat Genet, Leuven - Belgium

^[9] Katholieke Univ Leuven, Lab Expt Oncol, Dept Oncol, Leuven - Belgium

^[10] Katholieke Univ Leuven, Lab Intens Care Med, Dept Cellular & Mol Med, Leuven - Belgium

^[11] Univ Campinas UNICAMP, Inst Biol, Lab Emerging Viruses, Dept Genet Microbiol & Immunol, Campinas - Brazil

^[12] Univ Campinas UNICAMP, Expt Med Res Cluster EMRC, Campinas - Brazil

^[13] Univ Hosp Leuven, Div Pediat Rheumatol, Leuven - Belgium

^[14] Univ Hosp Leuven, European Reference Network Rare Immunodeficiency, Leuven - Belgium

^[15] Katholieke Univ Leuven, Lab Resp Dis & Thorac Surg BREATHE, Dept Chron Dis & Metab, Leuven - Belgium

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL & TRANSLATIONAL IMMUNOLOGY; v. 10, n. 4 2021.
• Citações Web of Science: 0

Resumo

Objectives Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. Methods Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils. Results Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10(-), immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils. Conclusion Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation. (AU)

• Processo FAPESP: 18/10990-1 - Caracterização e potencial terapêutico de quimiocinas em sepse e encefalite induzida por Flavivirus
• Beneficiário: Rafael Elias Marques Pereira Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular