By contrast, recruitment of LC3 to Listeria-containing phagosomes by LAP markedly enhances anti-listerial activity of macrophages and immunity of mice. Consequently, canonical autophagy does not contribute to anti-listerial activity of macrophages.

Cytosolic Listeria avoid targeting by canonical autophagy by surrounding themselves, in a process mediated by the virulence factor ActA, with a halo of host actin and by stalling phagophore assembly via PlcA/B.

Listeria use their virulence factors LLO and PlcA/B to destroy the membrane of conventional phagosomes before these can fuse with lysosomes, and then colonize the cytosol. Moreover, we have elucidated the molecular mechanisms that trigger LAP of Listeria and identified the integrin ITGAM-ITGB2/Mac-1/CR3/integrin α Mß 2 as the receptor that initiates LAP in response to Listeria infection. 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. Recently, using an in vivo mouse infection model, we have been able to demonstrate that Listeria in tissue macrophages are targeted exclusively by 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. Listeria are targeted both by canonical autophagy and by a noncanonical form of autophagy referred to as LC3-associated phagocytosis (LAP). The macroautophagic/autophagic machinery cannot only target cell-endogenous components but also intracellular pathogenic bacteria such as Listeria monocytogenes.

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