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Article ; Online: The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?

McKechnie, Julia L / Blish, Catherine A

2020 Volume 27, Issue 6, Page(s) 863–869

Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.
MeSH term(s)	COVID-19 ; Complement System Proteins/immunology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Cytokines/immunology ; Humans ; Immunity, Innate ; Killer Cells, Natural/immunology ; Myeloid Cells/immunology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology
Chemical Substances	Cytokines ; Complement System Proteins (9007-36-7)
Keywords	covid19
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2020.05.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Innate Immune System

McKechnie, Julia L. / Blish, Catherine A.

Cell Host & Microbe

Fighting on the Front Lines or Fanning the Flames of COVID-19?

2020 Volume 27, Issue 6, Page(s) 863–869

Keywords	Microbiology ; Parasitology ; Virology ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	2278004-X
ISSN	1931-3128
ISSN	1931-3128
DOI	10.1016/j.chom.2020.05.009
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?

McKechnie, Julia L / Blish, Catherine A

Abstract	The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #324343
Database	COVID19

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Article ; Online: Virus-like particle displaying SARS-CoV-2 receptor binding domain elicits neutralizing antibodies and is protective in a challenge model

McKechnie, Julia L / Fiala, Brooke / Wolf, Clancey / Ellis, Daniel / Holtzman, Douglas / Feldhaus, Andrew

bioRxiv

Abstract: While the effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has largely been successful, particularly in the developed world, the rise of new variants as well as waning immunity illustrate the need for a new ... ...

Abstract	While the effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has largely been successful, particularly in the developed world, the rise of new variants as well as waning immunity illustrate the need for a new generation of vaccines that provide broader and/or more durable protection against infection and severe disease. Here we describe the generation and characterization of IVX-411, a computationally designed, two-component virus-like particle (VLP) displaying the ancestral SARS-CoV-2 receptor binding domain (RBD) on its surface. Immunization of mice with IVX-411 generates neutralizing antibodies against the ancestral strain as well as three variants of concern. Neutralizing antibody titers elicited by IVX-411 are durable and significantly higher than those elicited by immunization with soluble RBD and spike antigens. Furthermore, immunization with IVX-411 is shown to be protective in a Syrian Golden hamster challenge model using two different strains of SARS-CoV-2. Overall, these studies demonstrate that IVX-411 is highly immunogenic and capable of eliciting broad, protective immunity.
Keywords	covid19
Language	English
Publishing date	2022-11-29
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.11.29.518404
Database	COVID19

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Article ; Online: Transgender identity in young people and adults recorded in UK primary care electronic patient records: retrospective, dynamic, cohort study.

McKechnie, Douglas Gordon John / O'Nions, Elizabeth / Bailey, Julia / Hobbs, Lorna / Gillespie, Frank / Petersen, Irene

BMJ medicine

2023 Volume 2, Issue 1, Page(s) e000499

Abstract: Objectives: To quantify the change in proportion of young people and adults identified as transgender in UK primary care records and to explore whether rates differ by age and socioeconomic deprivation.: Design: Retrospective, dynamic, cohort study.!# ...

Abstract	Objectives: To quantify the change in proportion of young people and adults identified as transgender in UK primary care records and to explore whether rates differ by age and socioeconomic deprivation. Design: Retrospective, dynamic, cohort study. Setting: IQVIA Medical Research Data, a database of electronic primary care records capturing data from 649 primary care practices in the UK between 1 January 2000 and 31 December 2018. Participants: 7 064 829 individuals aged 10-99 years, in all four UK countries. Main outcome measures: Diagnostic codes indicative of transgender identity were used. Sex assigned at birth was estimated by use of masculinising or feminising medication and procedural/diagnostic codes. Results: 2462 (0.03%) individuals had a record code indicating a transgender identity. Direction of transition could be estimated for 1340 (54%) people, of which 923 were assigned male at birth, and 417 were assigned female at birth. Rates of recording in age groups diverged substantially after 2010. Rates of the first recording of codes were highest in ages 16-17 years (between 2010 and 2018: 24.51/100 000 person years (95% confidence interval 20.95 to 28.50)). Transgender codes were associated with deprivation: the rate of the first recording was 1.59 (95% confidence interval 1.31 to 1.92) in the most deprived group in comparison with the least deprived group. Additionally, the rate ratio of the proportion of people who identified as transgender was 2.45 (95% confidence interval 2.28 to 2.65) in the most deprived group compared with the least deprived group. Substantial increases were noted in newly recorded transgender codes over time in all age groups (1.45/100 000 person years in 2000 (95% confidence interval 0.96 to 2.10) to 7.81/100 000 person years in 2018 (6.57 to 9.22)). In 2018, the proportion of people with transgender identity codes was highest in the age groups 16-17 years (16.23 per 10 000 (95% confidence interval 12.60 to 20.57)) and 18-29 years (12.42 per 10 000 (11.06 to 13.90)). Conclusion: The rate of transgender identity recorded in primary care records has increased fivefold from 2000 to 2018 and is highest in the 16-17 and 18-29 age groups. Transgender diagnostic coding is associated with socioeconomic deprivation and further work should investigate this association. Primary and specialist care should be commissioned accordingly to provide for the gender specific and general health needs of transgender people.
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Journal Article
ISSN	2754-0413
ISSN (online)	2754-0413
DOI	10.1136/bmjmed-2023-000499
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mass Cytometry Analysis of the NK Cell Receptor-Ligand Repertoire Reveals Unique Differences between Dengue-Infected Children and Adults.

McKechnie, Julia L / Beltrán, Davis / Ferreira, Anne-Maud M / Vergara, Rosemary / Saenz, Lisseth / Vergara, Ofelina / Estripeaut, Dora / Araúz, Ana B / Simpson, Laura J / Holmes, Susan / López-Vergès, Sandra / Blish, Catherine A

ImmunoHorizons

2020 Volume 4, Issue 10, Page(s) 634–647

Abstract: Dengue virus (DENV) is a significant cause of morbidity in many regions of the world, with children at the greatest risk of developing severe dengue. NK cells, characterized by their ability to rapidly recognize and kill virally infected cells, are ... ...

Abstract	Dengue virus (DENV) is a significant cause of morbidity in many regions of the world, with children at the greatest risk of developing severe dengue. NK cells, characterized by their ability to rapidly recognize and kill virally infected cells, are activated during acute DENV infection. However, their role in viral clearance versus pathogenesis has not been fully elucidated. Our goal was to profile the NK cell receptor-ligand repertoire to provide further insight into the function of NK cells during pediatric and adult DENV infection. We used mass cytometry to phenotype isolate NK cells and PBMCs from a cohort of DENV-infected children and adults. Using unsupervised clustering, we found that pediatric DENV infection leads to a decrease in total NK cell frequency with a reduction in the percentage of CD56
MeSH term(s)	Adolescent ; Adult ; Antibodies, Monoclonal/immunology ; Biomarkers ; CD57 Antigens/immunology ; Child ; Child, Preschool ; Dengue/blood ; Dengue/immunology ; Fas Ligand Protein/metabolism ; Female ; Flow Cytometry/methods ; Humans ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; Male ; Middle Aged ; Perforin/metabolism ; Receptors, Natural Killer Cell/immunology ; Staining and Labeling ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Biomarkers ; CD57 Antigens ; Fas Ligand Protein ; Receptors, Natural Killer Cell ; Perforin (126465-35-8)
Language	English
Publishing date	2020-10-16
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2000074
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Profiling of the Human Natural Killer Cell Receptor-Ligand Repertoire.

Vendrame, Elena / McKechnie, Julia L / Ranganath, Thanmayi / Zhao, Nancy Q / Rustagi, Arjun / Vergara, Rosemary / Ivison, Geoffrey T / Kronstad, Lisa M / Simpson, Laura J / Blish, Catherine A

Journal of visualized experiments : JoVE

2020 , Issue 165

Abstract: Natural killer (NK) cells are among the first responders to viral infections. The ability of NK cells to rapidly recognize and kill virally infected cells is regulated by their expression of germline-encoded inhibitory and activating receptors. The ... ...

Abstract	Natural killer (NK) cells are among the first responders to viral infections. The ability of NK cells to rapidly recognize and kill virally infected cells is regulated by their expression of germline-encoded inhibitory and activating receptors. The engagement of these receptors by their cognate ligands on target cells determines whether the intercellular interaction will result in NK cell killing. This protocol details the design and optimization of two complementary mass cytometry (CyTOF) panels. One panel was designed to phenotype NK cells based on receptor expression. The other panel was designed to interrogate expression of known ligands for NK cell receptors on several immune cell subsets. Together, these two panels allow for the profiling of the human NK cell receptor-ligand repertoire. Furthermore, this protocol also details the process by which we stain samples for CyTOF. This process has been optimized for improved reproducibility and standardization. An advantage of CyTOF is its ability to measure over 40 markers in each panel, with minimal signal overlap, allowing researchers to capture the breadth of the NK cell receptor-ligand repertoire. Palladium barcoding also reduces inter-sample variation, as well as consumption of reagents, making it easier to stain samples with each panel in parallel. Limitations of this protocol include the relatively low throughput of CyTOF and the inability to recover cells after analysis. These panels were designed for the analysis of clinical samples from patients suffering from acute and chronic viral infections, including dengue virus, human immunodeficiency virus (HIV), and influenza. However, they can be utilized in any setting to investigate the human NK cell receptor-ligand repertoire. Importantly, these methods can be applied broadly to the design and execution of future CyTOF panels.
MeSH term(s)	Antibodies/metabolism ; Cell Line ; DNA/metabolism ; Freeze Drying ; Humans ; Intercalating Agents/metabolism ; Killer Cells, Natural/immunology ; Ligands ; Receptors, Natural Killer Cell/metabolism ; Reproducibility of Results ; Staining and Labeling
Chemical Substances	Antibodies ; Intercalating Agents ; Ligands ; Receptors, Natural Killer Cell ; DNA (9007-49-2)
Language	English
Publishing date	2020-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61912
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: HLA Upregulation During Dengue Virus Infection Suppresses the Natural Killer Cell Response.

McKechnie, Julia L / Beltrán, Davis / Pitti, Arcelys / Saenz, Lisseth / Araúz, Ana B / Vergara, Rosemary / Harris, Eva / Lanier, Lewis L / Blish, Catherine A / López-Vergès, Sandra

Frontiers in cellular and infection microbiology

2019 Volume 9, Page(s) 268

Abstract: Dengue virus (DENV) is the most prevalent mosquito-borne virus in the world and a major cause of morbidity in the tropics and subtropics. Upregulation of HLA class I molecules has long been considered a feature of DENV infection, yet this has not been ... ...

Abstract	Dengue virus (DENV) is the most prevalent mosquito-borne virus in the world and a major cause of morbidity in the tropics and subtropics. Upregulation of HLA class I molecules has long been considered a feature of DENV infection, yet this has not been evaluated in the setting of natural infection. Natural killer (NK) cells, an innate immune cell subset critical for mounting an early response to viral infection, are inhibited by self HLA class I, suggesting that upregulation of HLA class I during DENV infection could dampen the NK cell response. Here we addressed whether upregulation of HLA class I molecules occurs during
MeSH term(s)	Cell Line ; Dengue/immunology ; Dengue/pathology ; Dengue Virus/growth & development ; Dengue Virus/immunology ; Gene Expression Profiling ; Histocompatibility Antigens Class I/biosynthesis ; Humans ; Immune Tolerance ; Immunity, Innate ; Killer Cells, Natural/immunology ; Monocytes/immunology ; Monocytes/virology ; Up-Regulation
Chemical Substances	Histocompatibility Antigens Class I
Language	English
Publishing date	2019-07-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2019.00268
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A single-cell atlas of the peripheral immune response to severe COVID-19.

Wilk, Aaron J / Rustagi, Arjun / Zhao, Nancy Q / Roque, Jonasel / Martinez-Colon, Giovanny J / McKechnie, Julia L / Ivison, Geoffrey T / Ranganath, Thanmayi / Vergara, Rosemary / Hollis, Taylor / Simpson, Laura J / Grant, Philip / Subramanian, Aruna / Rogers, Angela J / Blish, Catherine A

medRxiv : the preprint server for health sciences

2020

Abstract: There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 ... ...

Abstract	There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.04.17.20069930
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Article ; Online: A single-cell atlas of the peripheral immune response in patients with severe COVID-19.

Wilk, Aaron J / Rustagi, Arjun / Zhao, Nancy Q / Roque, Jonasel / Martínez-Colón, Giovanny J / McKechnie, Julia L / Ivison, Geoffrey T / Ranganath, Thanmayi / Vergara, Rosemary / Hollis, Taylor / Simpson, Laura J / Grant, Philip / Subramanian, Aruna / Rogers, Angela J / Blish, Catherine A

Nature medicine

2020 Volume 26, Issue 7, Page(s) 1070–1076

Abstract: There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people ... ...

Abstract	There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Betacoronavirus/immunology ; COVID-19 ; Case-Control Studies ; Coronavirus Infections/genetics ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Cytokines/genetics ; Cytokines/metabolism ; Female ; Gene Expression Profiling/methods ; Humans ; Immunity, Cellular ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/virology ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/genetics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; RNA-Seq/methods ; SARS-CoV-2 ; Sequence Analysis, RNA/methods ; Severity of Illness Index ; Single-Cell Analysis/methods ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Young Adult
Chemical Substances	Cytokines
Keywords	covid19
Language	English
Publishing date	2020-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-020-0944-y
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