Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 11, Pages 7558-7564Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.11.7558
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Funding
- NATIONAL CANCER INSTITUTE [T32CA009537] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI052286, R01AI025032, R01AI032972, K08AI065878, R37AI025032] Funding Source: NIH RePORTER
- Howard Hughes Medical Institute [56005710] Funding Source: Medline
- NCI NIH HHS [T32 CA009537, T32CA009537] Funding Source: Medline
- NIAID NIH HHS [R37 AI025032, AI065878, K08 AI065878, R01 AI025032-24, R37 AI025032-19, K08 AI065878-04, AI032972, R01 AI052286-10, R01 AI052286, R01 AI032972-20, R01 AI025032, R01 AI032972, R01 AI032972-15, AI052286, AI025032] Funding Source: Medline
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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-1 beta 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 I activation through multiple Nod-like receptors, including 1paf 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 I 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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