Repeated exposures to PM_2.5 alter the mitochondria and the influenza-mediated interferon response in an air-liquid...

Area of Science:

• Environmental Health
• Infectious Disease Immunology
• Respiratory Medicine

Background:

• Epidemiological studies link fine atmospheric particles (PM2.5) exposure to increased viral infection severity.
• In vitro studies on repeated PM2.5 exposure effects are limited, despite reflecting real-world human exposure.
• Understanding PM2.5's impact on antiviral responses is crucial for public health.

Purpose of the Study:

• To investigate the effects of repeated PM2.5 exposure on an in vitro bronchial epithelium model.
• To assess modulations of antiviral responses, specifically the interferon (IFN) pathway, after PM2.5 exposure prior to influenza A virus (IAV) infection.

Main Methods:

• Utilized an in vitro bronchial epithelium model at the air-liquid interface (ALI).
• Performed repeated exposures to Paris-collected PM2.5.
• Infected the model with influenza A virus (IAV) post-exposure and analyzed antiviral responses, including IFN pathway, inflammation, mitochondrial function, and autophagy.

Main Results:

• Demonstrated PM2.5 particle internalization and sustained pro-inflammatory response during repeated exposures.
• Observed a downregulation of the interferon (IFN) pathway following repeated PM2.5 exposure before IAV infection.
• Identified mitochondrial dysfunction and autophagic flux blockage, indicated by accumulated autophagic vesicles and p62 protein.

Conclusions:

• Repeated PM2.5 exposure impairs the airway's antiviral defense, specifically the IFN pathway, in an in vitro model.
• Mitochondrial alterations and/or blocked autophagic flux are implicated in the modulation of IFN signaling.
• Further research is warranted to elucidate the precise mechanisms linking PM2.5 exposure, cellular dysfunction, and impaired antiviral immunity.