Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection.
Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2797616?pdf=render |
| _version_ | 1811242596622663680 |
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| author | Nicole Meyer-Morse Jennifer R Robbins Chris S Rae Sofia N Mochegova Michele S Swanson Zijiang Zhao Herbert W Virgin Daniel Portnoy |
| author_facet | Nicole Meyer-Morse Jennifer R Robbins Chris S Rae Sofia N Mochegova Michele S Swanson Zijiang Zhao Herbert W Virgin Daniel Portnoy |
| author_sort | Nicole Meyer-Morse |
| collection | DOAJ |
| description | Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.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-/-). 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 microtubule-associated 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-/- mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5-/- BMDMs.We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs. |
| first_indexed | 2024-04-12T13:53:29Z |
| format | Article |
| id | doaj.art-dad4250e5fa1470d9d2460553f5e6cea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T13:53:29Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dad4250e5fa1470d9d2460553f5e6cea2022-12-22T03:30:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e861010.1371/journal.pone.0008610Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection.Nicole Meyer-MorseJennifer R RobbinsChris S RaeSofia N MochegovaMichele S SwansonZijiang ZhaoHerbert W VirginDaniel PortnoyRecent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.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-/-). 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 microtubule-associated 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-/- mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5-/- BMDMs.We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs.http://europepmc.org/articles/PMC2797616?pdf=render |
| spellingShingle | Nicole Meyer-Morse Jennifer R Robbins Chris S Rae Sofia N Mochegova Michele S Swanson Zijiang Zhao Herbert W Virgin Daniel Portnoy Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. PLoS ONE |
| title | Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. |
| title_full | Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. |
| title_fullStr | Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. |
| title_full_unstemmed | Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. |
| title_short | Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. |
| title_sort | listeriolysin o is necessary and sufficient to induce autophagy during listeria monocytogenes infection |
| url | http://europepmc.org/articles/PMC2797616?pdf=render |
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