LC3-associated phagocytosis initiated by integrin Mac-1 enhances immunity to Listeria monocytogenes

What is it about?

The macroautophagic/autophagic machinery cannot only target cell-endogenous components but also intracellular pathogenic bacteria such as Listeria monocytogenes. Listeria are targeted both by canonical autophagy and by a noncanonical form of autophagy referred to as LC3-associated phagocytosis (LAP). The molecular mechanisms involved and whether these processes contribute to anti-listerial immunity or rather provide Listeria with a replicative niche for persistent infection, however, remained unknown. Recently, using an in vivo mouse infection model, we have been able to demonstrate that Listeria in tissue macrophages are targeted exclusively by LAP. Furthermore, our data show that LAP is required for killing of Listeria by macrophages and thereby contributes to anti-listerial immunity of mice, whereas canonical autophagy is completely dispensable. Moreover, we have elucidated the molecular mechanisms that trigger LAP of Listeria and identified the integrin ITGAM-ITGB2/Mac-1/CR3/integrin αMß2 as the receptor that initiates LAP in response to Listeria infection.

Featured Image

Why is it important?

Our work highlights LAP as a particularly bactericidal form of phagocytosis. Nonetheless, only a subpopulation of approximately 20–25% of phagocytosed Listeria is targeted by LAP. Why not all phagocytosed Listeria are targeted by LAP and how macrophages decide which Listeria are to be targeted by LAP and which not, remain open questions. Perspectively, our data indicate that increasing the relative contribution of LAP to phagocytosis may be a promising strategy to enhance immunity to bacterial infection.