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

Scientific reports (2013-10-08)
Jens Möller, Tessa Lühmann, Mamta Chabria, Heike Hall, Viola Vogel
ABSTRACT

To clear pathogens from host tissues or biomaterial surfaces, phagocytes have to break the adhesive bacteria-substrate interactions. Here we analysed the mechanobiological process that enables macrophages to lift-off and phagocytose surface-bound Escherichia coli (E. coli). In this opsonin-independent process, macrophage filopodia hold on to the E. coli fimbriae long enough to induce a local protrusion of a lamellipodium. Specific contacts between the macrophage and E. coli are formed via the glycoprotein CD48 on filopodia and the adhesin FimH on type 1 fimbriae (hook). We show that bacterial detachment from surfaces occurrs after a lamellipodium has protruded underneath the bacterium (shovel), thereby breaking the multiple bacterium-surface interactions. After lift-off, the bacterium is engulfed by a phagocytic cup. Force activated catch bonds enable the long-term survival of the filopodium-fimbrium interactions while soluble mannose inhibitors and CD48 antibodies suppress the contact formation and thereby inhibit subsequent E. coli phagocytosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
RNase B Glycoprotein Standard from bovine pancreas, Proteomics Grade
Sigma-Aldrich
ExtrAvidin®−Cy3, buffered aqueous solution

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