<i>Listeria monocytogenes</i> triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy

Gabriel Mitchell, Mandy I. Cheng, Chen Chen, Brittney N. Nguyen, Aaron T. Whiteley, Sara Kianian, Jeffery S. Cox, Douglas R. Green, Kent McDonald, Daniel A. Portnoy

Proceedings of the National Academy of Sciences · 2017 · 93 citations · 38 references

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Abstract

Significance Autophagy mediates the routing of cytoplasmic components to degradative membrane-bound compartments. During infection by intracellular pathogens, autophagy proteins orchestrate several antimicrobial responses by marking pathogen-containing vacuoles and protecting the host cytosol from invaders. However, intracellular pathogens such as Listeria monocytogenes circumvent the autophagy machinery to promote pathogenesis. By combining bacterial and host mutants, we have dissected the role of two distinct autophagy-related processes in controlling L. monocytogenes growth in macrophages. Our results showed that L. monocytogenes is oblivious to the initial marking of its vacuole by autophagy proteins, but that subsequent autophagic targeting restricts bacterial growth in the host cytosol. We suggest that processes coordinated by the autophagy machinery constitute a multilayered network of cell-autonomous defenses.

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