Macrophage migration inhibitory factor enhances influenza-associated mortality in mice

Area of Science:

• Immunology
• Virology
• Respiratory Medicine

Background:

• Annual influenza epidemics cause significant mortality despite antiviral treatments.
• Host immune responses are crucial for controlling influenza virus infection.
• The role of macrophage migration inhibitory factor (MIF) in influenza pathogenesis is not well understood.

Purpose of the Study:

• To investigate the role of macrophage migration inhibitory factor (MIF) in influenza viral infection.
• To determine if targeting MIF can serve as a therapeutic strategy against influenza.

Main Methods:

• Utilized Mif-deficient mice, wild-type (WT) mice, and transgenic (Tg) mice overexpressing MIF.
• Administered antibody-mediated blockade of MIF in WT mice during infection.
• Analyzed lung inflammation, viral load, mortality, mitophagy protein levels (parkin), and type I/III interferon (IFN) responses.
• Conducted in vitro assays using human lung epithelial cells and recombinant human MIF.

Main Results:

• Mif-deficient mice exhibited reduced inflammation, viral load, and mortality compared to WT controls.
• Tg mice overexpressing MIF showed increased inflammation, viral load, and mortality.
• Antibody blockade of MIF improved survival in WT mice during influenza infection.
• Mif-deficient lungs had lower parkin levels and augmented antiviral IFN responses post-infection.
• In vitro, recombinant human MIF increased influenza virus infection in lung epithelial cells.

Conclusions:

• Macrophage migration inhibitory factor (MIF) impairs host antiviral immunity and exacerbates inflammation during influenza infection.
• Targeting MIF represents a potential therapeutic approach to mitigate influenza virus disease burden.