Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Human rhinovirus (HRV) exacerbates chronic obstructive pulmonary disease (COPD).
• COPD involves macrophages with impaired phagocytosis, but HRV's effect on this is unknown.
• Macrophages are crucial for pathogen clearance in the lungs.

Purpose of the Study:

• To investigate how human rhinovirus 16 impacts macrophage phagocytic function.
• To identify the molecular mechanisms by which HRV interferes with bacterial uptake in macrophages.

Main Methods:

• Macrophage cultures infected with human rhinovirus 16.
• Assays for bacterial uptake and receptor-mediated phagocytosis.
• Analysis of F-actin dynamics and Arpin expression.
• Gene silencing and re-expression techniques.

Main Results:

• Human rhinovirus 16 significantly impairs bacterial uptake and phagocytosis in macrophages.
• Infected cells show stalled phagocytic cups with accumulated F-actin.
• HRV 16 downregulates the expression of Arpin, a crucial regulator of the Arp2/3 complex.
• Arpin re-expression restores normal phagocytic function in HRV 16-infected cells.
• Arpin is essential for F-actin cup formation and phagosome completion.

Conclusions:

• Human rhinovirus 16 targets Arpin, a central actin regulator, to inhibit phagocytosis in macrophages.
• This viral mechanism allows HRV to perturb bacterial internalisation, potentially worsening COPD exacerbations.
• Arpin plays a critical role in multiple stages of the phagocytic process.