Listeria and autophagy escape

Abstract

Autophagy is a cell-autonomous mechanism of innate immunity that protects the cytosol against bacterial infection. Invasive bacteria, including Listeria monocytogenes, have thus evolved strategies to counteract a process that limits their intracellular growth. ActA is a surface protein produced by L. monocytogenes to polymerize actin and mediate intra- and intercellular movements, which plays a critical role in autophagy escape. We have recently investigated the role of another L. monocytogenes surface protein, the internalin InlK, in the infection process. We showed that in the cytosol of infected cells, InlK interacts with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoprotein particles named vaults. Although MVP has been implicated in a variety of key cellular process, its role remains elusive. We demonstrated that L. monocytogenes is able, via InlK, to decorate its surface with MVP in order to escape autophagic recognition. Strikingly, this new strategy used by L. monocytogenes to avoid autophagy is independent of ActA, suggesting that InlK-MVP interactions and actin polymerization are two processes that favor in the same manner the infection process. Understanding the role of MVP may provide new insights into bacterial infection and autophagy.

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Figures and Tables

Figure 1 Strategies used by L. monocytogenes to avoid autophagic recognition. Listeria is able to avoid autophagic recognition using two independent virulence factors, ActA and InlK. Depending on ActA and InlK expression, four possibilities can be distinguished: (1) ActA and InlK are coexpressed by the bacterium: InlK recruits MVP (red) to the surface of the bacterium. ActA subsequently replaces InlK, and actin (green) replaces MVP to disguise the bacteria and prevent ubiquitinated protein (Ub) recruitment/formation, p62 recognition and LC3 recruitment; (2) neither ActA nor InlK is expressed: Listeria is surrounded by ubiquitinated proteins, p62 and LC3, leading to autophagy; (3) In the absence of ActA, InlK recruits MVP and efficiently protects bacteria from ubiquitinated protein recruitment/formation, p62 recognition and LC3 recruitment; (4) ActA is expressed, but not InlK: the recruitment of the Arp2/3 complex and actin is sufficient to prevent ubiquitinated protein recruitment/formation, p62 recognition and LC3 recruitment.

Punctum to: Dortet L, Mostowy S, Samba Louaka A, Gouin E, Nahori MA, Wiemer EAC, et al. Recruitment of the Major Vault Protein by InlK: a Listeria monocytogenes strategy to avoid autophagy. PLoS Pathog 2011; 7:e1002168; PMID: 21829365; http://dx.doi.org/10.1371/journal.ppat.1002168

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