Listeria monocytogenes Evades Killing by Autophagy During Colonization of Host Cells

Cheryl L. Birmingham, Veronica Canadien, Edith Gouin, Erin B. Troy, Tamotsu Yoshimori, Pascale Cossart, Darren E. Higgins and John H. Brumell

volume 3 | issue 5

September/October 2007
Pages: 442 - 451

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Listeria monocytogenes is an intracellular pathogen that is able to colonize the cytosol of macrophages. Here we examined the interaction of this pathogen with autophagy, a host cytosolic degradative pathway that constitutes an important component of innate immunity towards microbial invaders. L. monocytogenes infection induced activation of the autophagy system in macrophages. At 1 h post infection (p.i.), a population of intracellular bacteria (~37%) colocalized with the autophagy marker LC3. These bacteria were within vacuoles and were targeted by autophagy in an LLO-dependent manner. At later stages in infection (by 4 h p.i.), the majority of L. monocytogenes escaped into the cytosol and rapidly replicated. At these times, less than 10% of intracellular bacteria colocalized with LC3. We found that ActA expression was sufficient to prevent autophagy of bacteria in the cytosol of macrophages. Surprisingly, ActA expression was not strictly necessary, indicating that other virulence factors were involved. Accordingly, we also found a role for the bacterial phospholipases, PI-PLC and PC-PLC, in autophagy evasion, as bacteria lacking phospholipase expression were targeted by autophagy at later times in infection. Together, our results demonstrate that L. monocytogenes utilizes multiple mechanisms to avoid destruction by the autophagy system during colonization of macrophages.

Authors

Cheryl L. Birmingham

University of Toronto

Veronica Canadien

Hospital for Sick Children

Edith Gouin

Institut Pasteur

Erin B. Troy

Harvard Medical School

Tamotsu Yoshimori

Department of Cellular Regulation; Research Institute for Microbial Diseases; Osaka University; Suita, Osaka Japan

Pascale Cossart