Unknown

Dataset Information

0

Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.


ABSTRACT: Legionella pneumophila (L. pneumophila), the causative agent of a severe form of pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. pneumophila infection except for the A/J, Nlrc4(-/-) (Ipaf(-/-)), and caspase-1(-/-) derived macrophages. Particularly, caspase-1 activation is detected during L. pneumophila infection of murine macrophages while absent in human cells. Recent in vitro experiments demonstrate that caspase-7 is cleaved by caspase-1. However, the biological role for caspase-7 activation downstream of caspase-1 is not known. Furthermore, whether this reaction is pertinent to the apoptosis or to the inflammation pathway or whether it mediates a yet unidentified effect is unclear. Using the intracellular pathogen L. pneumophila, we show that, upon infection of murine macrophages, caspase-7 was activated downstream of the Nlrc4 inflammasome and required caspase-1 activation. Such activation of caspase-7 was mediated by flagellin and required a functional Naip5. Remarkably, mice lacking caspase-7 and its macrophages allowed substantial L. pneumophila replication. Permissiveness of caspase-7(-/-) macrophages to the intracellular pathogen was due to defective delivery of the organism to the lysosome and to delayed cell death during early stages of infection. These results reveal a new mechanism for caspase-7 activation downstream of the Nlrc4 inflammasome and present a novel biological role for caspase-7 in host defense against an intracellular bacterium.

SUBMITTER: Akhter A 

PROVIDER: S-EPMC2657210 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications


Legionella pneumophila (L. pneumophila), the causative agent of a severe form of pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. pneumophila infection except for the A/J, Nlrc4(-/-) (Ipaf(-/-)), and caspase-1(-/-) derived macrophages. Particularly, caspase-1 activation is detected during L. pneumophila infection of murine macrophages while absent in human cells. Recent in vitro experiments demonstrate that cas  ...[more]

Similar Datasets

| S-EPMC6622555 | biostudies-literature
| S-EPMC2150987 | biostudies-literature
| S-EPMC1584282 | biostudies-literature
| S-EPMC3269931 | biostudies-literature
| S-EPMC3797225 | biostudies-literature
| S-EPMC5542441 | biostudies-literature
| S-EPMC3751498 | biostudies-literature
| S-EPMC3340363 | biostudies-literature
| S-EPMC6792017 | biostudies-literature
| S-SCDT-EMBOJ-2018-101266 | biostudies-other