The β2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F. Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the β2 integrin Mac-1 (CR3, integrin αMβ2), a receptor recognizing diverse microbial ligands. Interaction of L.m. with Mac-1 induces acid sphingomyelinase-mediated changes in membrane lipid composition that facilitate assembly and activation of the phagocyte NAPDH oxidase Nox2. Nox2-derived reactive oxygen species then trigger LC3 recruitment to L.m.-containing phagosomes by LAP. By promoting fusion of L.m.-containing phagosomes with lysosomes, LAP increases exposure of L.m. to bactericidal acid hydrolases, thereby enhancing anti-listerial activity of macrophages and immunity of mice.

Graphical abstract

Teaser

Listeria monocytogenes are targeted by the autophagic machinery via unclear molecular mechanisms. Gluschko and Herb et al. demonstrate that LC3-associated phagocytosis, but not canonical autophagy, is required for elimination of L. monocytogenes by macrophages and activated by the β2 integrin Mac-1 (CR3, integrin αMβ2).


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