Macrophages lift off surface-bound bacteria using a filopodium-lamellipodium hook-and-shovel mechanism

Area of Science:

• Cellular and Molecular Biology
• Immunology
• Biophysics

Background:

• Phagocytes must overcome adhesive bacterial-substrate interactions to clear pathogens.
• Understanding the mechanobiology of bacterial detachment is crucial for host defense.
• Escherichia coli (E. coli) employs fimbriae for surface adhesion.

Purpose of the Study:

• To elucidate the mechanobiological mechanisms macrophages use to detach and phagocytose surface-bound E. coli.
• To investigate the role of specific molecular interactions in bacterial lift-off.
• To characterize the opsonin-independent phagocytosis pathway.

Main Methods:

• Analysis of macrophage-E. coli interactions using advanced microscopy.
• Investigation of molecular interactions involving CD48 and FimH.
• Functional assays with mannose inhibitors and CD48 antibodies.

Main Results:

• Macrophages utilize filopodia to engage E. coli fimbriae, initiating lamellipodium protrusion.
• A 'shoveling' mechanism by the lamellipodium detaches bacteria from the surface.
• CD48 on macrophages and FimH on E. coli mediate crucial adhesive interactions.
• Force-activated catch bonds stabilize filopodium-fimbrium interactions.

Conclusions:

• Macrophage phagocytosis of surface-bound E. coli is a mechanobiological process involving filopodia, lamellipodia, and specific molecular adhesions.
• The CD48-FimH interaction and force-activated catch bonds are key for bacterial detachment.
• This opsonin-independent pathway highlights a critical host defense mechanism against bacterial colonization.