Trafficking of Lymphocyte Subsets in Host Defense and Immunopathogenesis in COVID-19

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

Selective expansion in the blood of lymphocyte subsets as defined by chemokine receptor expression can be used to infer activities for these cells in defense and/or pathology, while selective depletion of subsets from blood in pneumonia and other disorders can be used to infer the migration of these cells and roles for their receptors in trafficking into tissue. In FY 2023 we have continued to analyze chemokine receptor expression on T, NK, and dendritic cells and monocytes in the blood of individuals hospitalized due to COVID-19 as compared to healthy donors using multi-parameter flow cytometry. We have identified decreased expression of several chemokine receptors on the T and/or NK cells in patients hospitalized with COVID-19. We have considered whether depletion of cells expressing a given chemokine receptor might be due to the activity of a co-expressed receptor, and we have examined changes in the expression of receptors on T cells expressing pairs of receptors to identify receptors that may be acting as drivers versus those that are passengers. We have conducted experiments in K18-hACE2 mice infected with SARS-CoV-2 to pursue the findings from the patient samples and to understand more generally the roles for the chemokine system in host defense and immunopathogenesis in an experimental model of infection. In these studies, we have found that one of the driver receptors in humans is critical for the trafficking of plasmacytoid dendritic cells into the lungs of infected mice. Human data have suggested that these cells, which produce large amounts of type 1 and type 3 interferons, are critical in host defense in COVID-19. At the same time, we have been using a mouse model of influenza infection to compare the roles of the chemokine system in this model with the findings following infection with SARS-CoV-2.