# Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity

## TL;DR

This paper reviews how influenza A virus uses cell death pathways to both fight the virus and cause lung damage, highlighting the need for better treatment strategies.

## Contribution

The paper provides a comprehensive review of IAV-induced programmed cell death mechanisms and their dual role in immunity and immunopathology.

## Key findings

- IAV activates multiple programmed cell death pathways that restrict viral spread but also damage lung tissue.
- Excessive cell death leads to disrupted epithelial barriers and severe inflammation, contributing to cytokine storms.
- Understanding these mechanisms could help develop therapies to reduce immunopathological damage in severe influenza.

## Abstract

Influenza A virus (IAV) infection activates multiple programmed cell death (PCD) pathways, which, while restricting viral replication and dissemination, concurrently disrupt the respiratory epithelial barrier and compromise immune homeostasis. Excessive activation of apoptosis, necroptosis, pyroptosis, and related processes results in tight junction(TJ) disruption, impaired mucociliary clearance and gas exchange, and amplification of inflammatory cascades, ultimately driving cytokine storm and severe tissue injury. This dual role of PCD underscores its importance in antiviral defense while exposing its potential to exacerbate immunopathology. Accordingly, this review focuses on IAV-induced PCD mechanisms, delineating their contribution to epithelial barrier breakdown and immune dysregulation, with the aim of informing strategies for precise modulation of immunopathological damage and improving therapeutic outcomes in severe influenza.