Your browser doesn't support javascript.
loading
NK Cell-Monocyte Cross-talk Underlies NK Cell Activation in Severe COVID-19.
Lee, Madeline J; de Los Rios Kobara, Izumi; Barnard, Trisha R; Vales Torres, Xariana; Tobin, Nicole H; Ferbas, Kathie G; Rimoin, Anne W; Yang, Otto O; Aldrovandi, Grace M; Wilk, Aaron J; Fulcher, Jennifer A; Blish, Catherine A.
Afiliação
  • Lee MJ; Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
  • de Los Rios Kobara I; Stanford Immunology Program, Stanford University School of Medicine, Palo Alto, CA.
  • Barnard TR; Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
  • Vales Torres X; Stanford Immunology Program, Stanford University School of Medicine, Palo Alto, CA.
  • Tobin NH; Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
  • Ferbas KG; Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
  • Rimoin AW; Stanford Immunology Program, Stanford University School of Medicine, Palo Alto, CA.
  • Yang OO; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
  • Aldrovandi GM; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
  • Wilk AJ; Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA.
  • Fulcher JA; Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
  • Blish CA; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
J Immunol ; 212(11): 1693-1705, 2024 Jun 01.
Article em En | MEDLINE | ID: mdl-38578283
ABSTRACT
NK cells in the peripheral blood of severe COVID-19 patients exhibit a unique profile characterized by activation and dysfunction. Previous studies have identified soluble factors, including type I IFN and TGF-ß, that underlie this dysregulation. However, the role of cell-cell interactions in modulating NK cell function during COVID-19 remains unclear. To address this question, we combined cell-cell communication analysis on existing single-cell RNA sequencing data with in vitro primary cell coculture experiments to dissect the mechanisms underlying NK cell dysfunction in COVID-19. We found that NK cells are predicted to interact most strongly with monocytes and that this occurs via both soluble factors and direct interactions. To validate these findings, we performed in vitro cocultures in which NK cells from healthy human donors were incubated with monocytes from COVID-19+ or healthy donors. Coculture of healthy NK cells with monocytes from COVID-19 patients recapitulated aspects of the NK cell phenotype observed in severe COVID-19, including decreased expression of NKG2D, increased expression of activation markers, and increased proliferation. When these experiments were performed in a Transwell setting, we found that only CD56bright CD16- NK cells were activated in the presence of severe COVID-19 patient monocytes. O-link analysis of supernatants from Transwell cocultures revealed that cultures containing severe COVID-19 patient monocytes had significantly elevated levels of proinflammatory cytokines and chemokines, as well as TGF-ß. Collectively, these results demonstrate that interactions between NK cells and monocytes in the peripheral blood of COVID-19 patients contribute to NK cell activation and dysfunction in severe COVID-19.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Ativação Linfocitária / Monócitos / Comunicação Celular / Técnicas de Cocultura / SARS-CoV-2 / COVID-19 Limite: Female / Humans / Male / Middle aged Idioma: En Revista: J Immunol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Ativação Linfocitária / Monócitos / Comunicação Celular / Técnicas de Cocultura / SARS-CoV-2 / COVID-19 Limite: Female / Humans / Male / Middle aged Idioma: En Revista: J Immunol Ano de publicação: 2024 Tipo de documento: Article