Natural killer cells as a determinant of coronavirus replication and pathogenicity
Poster, ITI Human Immune Monitoring Technology and Bioinformatics Conference, Stanford, CA
Talks and presentations
Interrogating the natural killer cell response to COVID-19: SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Poster, Cell Symposium: Viruses in Health and Disease, Sitges, Spain
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.
SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Talk, Stanford Immunology Scientific Conference, Monterey, California
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.
Interrogating the natural killer cell response to COVID-19
Talk, Fred Hutch Immunology Graduate Student Symposium, Seattle, WA
Interrogating the natural killer cell response to COVID-19: SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Poster, NK2022, Bonita Springs, FL
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.
Assessing the impact of COVID-19 on NK cells
Poster, Midwinter Conference of Immunology, Monterey, CA
Severe COVID-19 induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. In order to better understand the NK cell response to this disease, we profiled NK cells and whole PBMC from donors across the COVID-19 severity spectrum using CyTOF, single-cell RNA sequencing, and single-cell ATAC sequencing. We found that severe COVID-19 induces strong activation of peripheral NK cells. The activated NK cells in severe COVID-19 patients also downregulate surface expression, but not transcriptional expression, of the activating receptors DNAM-1 and NKG2D. As both of these receptors can be internalized upon ligation, we assessed expression of the ligands for these receptors on other peripheral immune cells and identified a significant increase in the expression of the ligands for NKG2D and DNAM-1 on the monocytes of severe COVID-19 patients. Collectively, our results suggest that monocytes may activate NK cells via the ligation of activating receptors in severe COVID-19.
Examining the memory-like responses of natural killer cells following activation by mature dendritic cells
Poster, Washington University Undergraduate Research Symposium, St. Louis, MO
Increasing Resistance to UV-B Radiation in Cyanobacteria
Poster, 2017 iGEM Jamboree, Boston, MA