1/8/2023 0 Comments Flowjo acquired by bdAlthough antigenic peptides presented by MHC-II molecules are thought to be mainly generated from extracellular sources intracellular antigens can also be presented by MHC-II molecules through non-classical pathways. 14 Mature DCs activate CD4 +T-cells and CD8 +T-cells by presenting antigens in association with major histocompatibility complex class II (MHC-II also known as human leukocyte antigen-DR isotype, HLA-DR) and MHC-I molecules, respectively. 1, 2, 7–12 Identification of the underlying cellular and molecular mechanisms is critical to guide the development of effective therapies.ĭendritic cells (DCs) are specialized antigen-presenting cells (APCs) that play a central role in priming and activating naïve T-cells. 3–13 Progression to severe/critical disease is linked to insufficient control of viral replication, persistent viral load, defective antiviral defense pathways, and excessive inflammation driven by an unbalanced immune response. However, some patients progress to a second phase where the disease becomes severe the clinical sequelae include immune dysfunction, lymphopenia, sustained inflammation, secondary bacterial infection, acute respiratory distress syndrome (ARDS), coagulation activation, thrombosis, myocardial injury, and hepatic and kidney injury. 1, 2 In the vast majority of patients, the disease is characterized by flu-like symptoms, which resolves after elimination of the infection (first/only phase). Keywords: SARS-CoV-2, COVID-19, inflammation, innate immunity, plasmacytoid dendritic cells, conventional dendritic cellsĬoronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can range in severity from asymptomatic to fatal disease. CD11c expression level on cDC2-like cells was significantly lower ( P=0.03) in non-survivors compared to survivors, and CD11c was inversely correlated with disease severity rating ( r=– 0.47, P=0.025).Ĭonclusion: A lower frequency of pDCs compared to other circulating DCs, and lower expression levels of HLA-DR, CD123 or CD11c on DCs is associated with fatal COVID-19. CD123 expression level on pDCs was significantly lower ( P=0.038) in non-survivors compared to survivors, and CD123 was inversely correlated with disease severity rating ( r=– 0.5, P=0.016). HLA-DR expression level on pDCs and cDC2-like cells was lower in non-survivors compared to survivors ( P=0.02 and P=0.058, respectively), and HLA-DR was inversely correlated with disease severity rating (pDCs: r= – 0.47, P=0.027 cDC2-like cells: r= – 0.45, P=0.037). The frequency of pDCs was significantly higher than cDC2-like cells ( P=0.0002) and pre-cDCs ( P< 0.0001) in survivors but not in non-survivors. Results: The ratio of pDCs to pre-cDCs was significantly lower ( P=0.0005) in non-survivors compared to survivors. ![]() Patients were followed-up during hospital admission and grouped into survivors (n=17) and non-survivors (n=5) of COVID-19. Peripheral whole blood was obtained during the 2 nd week of illness, stained with antibodies specific for lineage markers, human leukocyte antigen-DR isotype (HLA-DR), CD11c, and CD123, and analyzed by flow cytometry. Patients and methods: Patients with COVID-19 were enrolled, and 22 were included in this study. We assessed the frequency and phenotype of pDCs and cDCs in survivors and non-survivors of COVID-19. Conventional DCs (cDCs) are critical for the elimination of viral infections owing to their specialized ability to prime and activate T cells. Plasmacytoid dendritic cells (pDCs) are specialized in the rapid production of interferons in response to viral infections, and can also prime and activate T-cells. ![]() Purpose: Severe coronavirus disease 2019 (COVID-19) is linked to insufficient control of viral replication and excessive inflammation driven by an unbalanced immune response. Amal Hasan, 1 Ebaa Al-Ozairi, 2, 3 Nosiba YM Hassan, 4 Shamsha Ali, 5 Rasheed Ahmad, 1 Nada Al-Shatti, 6 Salem Alshemmari, 3, 7 Fahd Al-Mulla 8ġDepartment of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait 2Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait 3Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait 4Department of Internal Medicine, Jaber Al-Ahmad Hospital, Ministry of Health, Kuwait City, Kuwait 5Special Services Facility, Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait 6Immunology & HLA Laboratory, Kuwait Cancer Control Center, Ministry of Health, Kuwait City, Kuwait 7Department of Hematology, Kuwait Cancer Control Center, Ministry of Health, Kuwait City, Kuwit 8Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait City, KuwaitĬorrespondence: Amal Hasan, Department of Immunology and Microbiology Dasman Diabetes Institute, Dasman, Kuwait, Tel +965 2224 2999 Ext.
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