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

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

For the human studies, we hypothesize that changes in relative and absolute numbers of blood lymphocyte subsets defined or characterized by chemokine receptor expression will help us to understand the roles for these lymphocyte subsets and particular chemokine receptors in host defense and pathogenesis during COVID-19. Selective expansion of lymphocyte subsets in blood can be used to infer a role in defense and/or pathology, while selective depletion of subsets from blood in pneumonia and other disorders can be used in addition to infer the migration of these cells into tissue. In FY 2021 we have analyzed chemokine receptor expression on T and NK cells in the blood of more than 20 individuals hospitalized due to COVID-19 as compared to healthy donors using multi-parameter flow cytometry. We have also collected plasma from these same samples for measuring levels of cytokines and chemokines to correlate changes in lymphocyte subsets as defined by chemokine receptors with the production of these factors. We have begun 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. At the same time, we have begun 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.