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Publication : Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection.

First Author  Warren SE Year  2008
Journal  J Immunol Volume  180
Issue  11 Pages  7558-64
PubMed ID  18490757 Mgi Jnum  J:136327
Mgi Id  MGI:3795996 Doi  10.4049/jimmunol.180.11.7558
Citation  Warren SE, et al. (2008) Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J Immunol 180(11):7558-64
abstractText  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.
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