title: Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection.
abstract: Listeria monocytogenes escapes from the phagosome of macrophages and replicates within the cytosolic compartment. The macrophage responds to L. monocytogenes through detection pathways located on the cell surface (TLRs) and within the cytosol (Nod-like receptors) to promote inflammatory processes aimed at clearing the pathogen. Cytosolic L. monocytogenes activates caspase 1, resulting in post-translational processing of the cytokines IL-1beta and IL-18 as well as caspase 1-dependent cell death (pyroptosis). We demonstrate that the presence of L. monocytogenes within the cytosolic compartment induces caspase 1 activation through multiple Nod-like receptors, including Ipaf and Nalp3. Flagellin expression by cytosolic L. monocytogenes was detected through Ipaf in a dose-dependent manner. Concordantly, detection of flagellin promoted bacterial clearance in a murine infection model. Finally, we provide evidence that suggests cytosolic L. monocytogenes activates caspase 1 through a third pathway, which signals through the adaptor protein ASC. Thus, L. monocytogenes activates caspase 1 in macrophages via multiple pathways, all of which detect the presence of bacteria within the cytosol.
authors.affiliation: Department of Immunology, University of Washington, Seattle WA 98195, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Warren
authors.forename: Dat P
authors.initials: DP
authors.lastname: Mao
authors.forename: April E
authors.initials: AE
authors.lastname: Rodriguez
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism*; D003600:Cytosol / Q000382:microbiology; D004789:Enzyme Activation; D005408:Flagellin / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism; D008088:Listeriosis / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D051193:Toll-Like Receptors; D005408:Flagellin; D020170:Caspase 1