Journal
AUTOPHAGY
Volume 9, Issue 7, Pages 985-995Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.24406
Keywords
autophagy; diacylglycerol; innate immunity; LC3; LC3-associated phagocytosis; Listeria monocytogenes; reactive oxygen species; ubiquitin
Categories
Funding
- Burroughs Wellcome Fund
- Canadian Foundation for Innovation
- Ontario Innovation Trust
- Canadian Institutes of Health Research
- NSERC PGS-D scholarship
- CIHR Training Fellowship [TGF-53877]
- Canadian Institutes of Health Research [MOP#97756]
- Arthritis Society of Canada [RG11/013]
- National Institutes of Health [AI053669]
Ask authors/readers for more resources
Listeria monocytogenes is a bacterial pathogen that can escape the phagosome and replicate in the cytosol of host cells during infection. We previously observed that a population (up to 35%) of L. monocytogenes strain 10403S colocalize with the macroautophagy marker LC3 at 1 h postinfection. This is thought to give rise to spacious Listeria-containing phagosomes (SLAPs), a membrane-bound compartment harboring slow-growing bacteria that is associated with persistent infection. Here, we examined the host and bacterial factors that mediate LC3 recruitment to bacteria at 1 h postinfection. At this early time point, LC3 bacteria were present within single-membrane phagosomes that are LAMP1(+). Protein ubiquitination is known to play a role in targeting cytosolic L. monocytogenes to macroautophagy. However, we found that neither protein ubiquitination nor the ubiquitin-binding adaptor SQSTM1/p62 are associated with LC3(+) bacteria at 1 h postinfection. Reactive oxygen species (ROS) production by the CYBB/NOX2 NADPH oxidase was also required for LC3(+) recruitment to bacteria at 1 h postinfection and for subsequent SLAP formation. Diacylglycerol is an upstream activator of the CYBB/NOX2 NADPH oxidase, and its production by both bacterial and host phospholipases was required for LC3 recruitment to bacteria. Our data suggest that the LC3-associated phagocytosis (LAP) pathway, which is distinct from macroautophagy, targets L. monocytogenes during the early stage of infection within host macrophages and allows establishment of an intracellular niche (SLAPs) associated with persistent infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available