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Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection
| Citations: | 2 - 0 self |
BibTeX
@MISC{Meyer-morse_listeriolysino,
author = {Nicole Meyer-morse and Jennifer R. Robbins and Chris S. Rae and Sofia N. Mochegova and Michele S. Swanson and Zijiang Zhao and Herbert W. Virgin and Daniel Portnoy},
title = {Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection},
year = {}
}
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Abstract
Background: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection. Methodology/Principal Findings: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5 2/2). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubuleassociated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5 2/2 mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5 2/2 BMDMs. Conclusions/Significance: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted
Keyphrases
listeria monocytogenes infection listeriolysin necessary mutant lacking llo autophagy activation mouse embryonic fibroblast methodology principal finding conclusion significance vacuolar escape measurable role lc3 colocalization membrane damage targeted autophagy cell type assayed pore forming activity microtubuleassociated protein protective mechanism related cytolysin autophagy subsequent recent study bone marrow primary vacuole escape defect variable effect cholesterol-dependent cytolysin listeriolysin intracellular growth lc3 lipidation
