I am conducting a study where I need to be able to identify LC3-associated Phagocytosis (LAP). I also want to know how to inhibit or activate LAP
Hey Patrick,
LAP is a relatively recently discovered cellular process during which some but not all components of the canonical autophagic machinery are used to recruit the autophagy protein ‘microtubule-associated protein 1A/1B light chain 3B’ (LC3) directly to the phagosomal membrane. These LC3-decorated phagosomes are called LAPosomes. In comparison to conventional phagosomes, LAPosomes show increased fusion with lysosomes and, therefore, have enhanced antimicrobial properties. How LAP is initiated is, however, incompletely understood. One of the key factors in LAP induction is for sure the production of reactive oxygen species (ROS) through the NADPH oxidase Nox2. So by inhibiting Nox2 activity (but please not by DPI) or by using Nox2-KO cells you can hinder LAP induction. To get an idea of analysis of LAP you can have a look at the following papers, if you like:
C, Münz. Autophagy in immunity. Progress in Molecular Biology and Translational Science. 2020, Chapter Autophagy in immunity
Gluschko, A. et al. The beta2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes. Cell Host Microbe. 2018 23, 324-337 e325.
Herb, M. et al. LC3-associated phagocytosis initiated by integrin ITGAM-ITGB2/Mac-1 enhances immunity to Listeria monocytogenes. Autophagy. 2018 14, 1462-1464.
Herb, M. et al. LC3-associated phagocytosis - The highway to hell for phagocytosed microbes. Semin Cell Dev Biol. 2020 101, 68-76.
Koster, S. et al. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc Natl Acad Sci U S A. 2017 114, E8711-E8720.
Martinez, J. et al. Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature. 2016 533, 115-119.
Martinez, J. et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol. 2015 17, 893-906.
Sanjuan, M.A. et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007 450, 1253-1257.
Schille, S. et al. LC3-associated phagocytosis in microbial pathogenesis. Int J Med Microbiol. 2018 308, 228-236.
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