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Co-Culture Systems to Study Epithelial-Immune Interactions During SARS-CoV-2 Infection.

Scott H Randell1, Katherine C Barnett2

  • 1Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

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|April 8, 2026
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Summary
This summary is machine-generated.

This study introduces two in vitro co-culture systems to investigate inflammatory cytokine responses during SARS-CoV-2 infection. These models facilitate the study of epithelial-immune cell interactions and cytokine release, like IL-1β and IL-6.

Keywords:
SARS‐CoV‐2human airway epitheliuminflammasomeinterleukin‐1βinterleukin‐6peripheral blood mononuclear cells

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects airway epithelial cells, not immune cells.
  • Immune cell cytokine responses to SARS-CoV-2 depend on interactions with infected epithelial cells.
  • Understanding epithelial-immune crosstalk is crucial for studying inflammatory responses in viral infections.

Purpose of the Study:

  • To describe two novel co-culture systems for studying SARS-CoV-2-induced inflammatory cytokine responses.
  • To enable investigation of epithelial-immune cell interactions in vitro.
  • To provide methods for analyzing cytokine release, including IL-1β and IL-6.

Main Methods:

  • Development of a partially primary co-culture system using SARS-CoV-2-infected Vero-E6 cells and human peripheral blood mononuclear cells (PBMCs).
  • Establishment of a primary human co-culture system with SARS-CoV-2-infected primary human airway epithelia (HAE) at an air-liquid interface (ALI) and human PBMCs.
  • Inclusion of protocols for cell culture, PBMC isolation and preparation, and the use of inhibitors to modulate cytokine responses.

Main Results:

  • Demonstration of two viable co-culture systems to study SARS-CoV-2 infection dynamics.
  • Observation of inflammasome-regulated cytokine (IL-1β) release in a Vero-E6 and PBMC co-culture.
  • Analysis of IL-1β and IL-6 crosstalk between infected HAE and PBMCs in a primary human co-culture system.

Conclusions:

  • The described co-culture systems provide valuable tools for in vitro research on SARS-CoV-2 pathogenesis.
  • These models allow for the detailed study of inflammatory cytokine production driven by epithelial-immune interactions.
  • The methods support the investigation of therapeutic interventions targeting cytokine responses during viral infections.