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 2022 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 correlated the expression of surface receptors with levels of their mRNAs. We have investigated roles for pro-inflammatory cytokines in regulating chemokine receptor expression, and we have performed in vitro experiments that support the hypothesis that changes in receptor expression on blood leukocytes reflects the use of these receptors for extravasation. We have measured levels of cytokines and chemokines to correlate changes in lymphocyte subsets as defined by chemokine receptors with the production of these factors. These studies have suggested roles for several chemokine receptors in the trafficking of T cells and dendritic cells into tissue in COVID-19. 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. 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.