Exploring Influenza A Virus-Induced Lung Injury and Immune Response Based on Humanized Lung-on-Chip

Area of Science:

• * Respiratory viral infections
• * Immunology
• * Systems biology

Background:

• * Influenza A virus poses a significant threat, causing widespread illness and death.
• * Understanding the host's cellular and molecular response is crucial for developing effective treatments.

Purpose of the Study:

• * To analyze the transcriptome characteristics of peripheral blood mononuclear cells (PBMCs) during influenza A virus infection.
• * To simulate influenza A virus infection using a human lung microarray model.
• * To investigate the role of immune cells in the lung's response to influenza.

Main Methods:

• * Construction of a human lung microarray model with alveolar epithelial cells, vascular endothelial cells, alveolar macrophages, and PBMCs.
• * Simulation of influenza A virus infection within the lung model.
• * Analysis of PBMC transcriptome using single-cell RNA sequencing.

Main Results:

• * The lung model accurately mimicked alveolar structure and function in vitro.
• * Influenza A virus infection induced inflammatory responses in epithelial cells and damaged endothelial cells, leading to barrier dysfunction.
• * Single-cell RNA sequencing revealed that B cells and CD4 T cells were key players, activating type I interferon and cytokine signaling pathways.

Conclusions:

• * Immune cell interactions are critical in endothelial cell injury and immune cell recruitment during influenza infection.
• * The lung-on-chip model combined with single-cell RNA sequencing offers a powerful platform for studying lung immunity to influenza.
• * This approach can aid in discovering novel therapeutic strategies for influenza.