Characterization of low-density granulocytes in COVID-19

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Cabrera , L E , Pekkarinen , P T , Alander , M , Nowlan , K H A , Nguyen , N A , Jokiranta , S , Kuivanen , S , Patjas , A , Mero , S , Pakkanen , S H , Heinonen , S , Kantele , A , Vapalahti , O , Kekäläinen , E & Strandin , T 2021 , ' Characterization of low-density granulocytes in COVID-19 ' , PLoS Pathogens , vol. 17 , no. 7 , 1009721 .

Title: Characterization of low-density granulocytes in COVID-19
Author: Cabrera, Luz E.; Pekkarinen, Pirkka T.; Alander, Maria; Nowlan, Kirsten H. A.; Nguyen, Ngoc Anh; Jokiranta, Suvi; Kuivanen, Suvi; Patjas, Anu; Mero, Sointu; Pakkanen, Sari H.; Heinonen, Santtu; Kantele, Anu; Vapalahti, Olli; Kekäläinen, Eliisa; Strandin, Tomas
Contributor organization: Department of Virology
Viral Zoonosis Research Unit
Research Programs Unit
Department of Bacteriology and Immunology
TRIMM - Translational Immunology Research Program
Children's Hospital
HUMI - Human Microbiome Research
University of Helsinki
Department of Diagnostics and Therapeutics
Faculty of Medicine
Department of Medicine
HUS Inflammation Center
Veterinary Biosciences
Helsinki One Health (HOH)
Olli Pekka Vapalahti / Principal Investigator
Veterinary Microbiology and Epidemiology
Date: 2021-07
Language: eng
Number of pages: 22
Belongs to series: PLoS Pathogens
ISSN: 1553-7366
Abstract: Author summary The emergence of SARS-COV-2 and the ensuing COVID-19 disease has revealed an unprecedented need to understand the pathological mechanisms of acute respiratory infections in more detail. Granulocytes are highly abundant cells of the innate immunity, and thus first responders towards acute infections. However, their excessive activation can cause unwanted tissue damage and detrimental effects in humans. This study identifies a population of low-density granulocytes (LDGs) in COVID-19 patient samples, which has been poorly described in the context of acute infections so far. These cells were subclassified and found to be mainly of immature phenotypes. Further characterization revealed COVID-19 LDGs as a phenotypically diverse population with immunosuppressive characteristics, which seemed to be in line with an elevated recruitment and activation of granulocytes. Altogether, these findings suggest LDG may play a role in COVID-19 disease progression. Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.
1182 Biochemistry, cell and molecular biology
11832 Microbiology and virology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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