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Cited by 193

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Caspase-7 Activation by the Nlrc4/Ipaf Inflammasome Restricts Legionella pneumophila Infection

Open access
Akhter, Anwari, Gavrilin, Mikhail A., Frantz, Laura, Washington, Songcerae, Ditty, Cameron, Limoli, Dominique, Day, Colby, Sarkar, Anasuya, Newland, Christie, Butchar, Jonathan, Marsh, Clay B., Wewers, Mark D., Tridandapani, Susheela, Kanneganti, Thirumala-Devi, Amer, Amal O.·2009·PLoS Pathogens

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.

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Metadata

Authors
Akhter, A., Gavrilin, M. A., Frantz, L., Washington, S., Ditty, C., Limoli, D., Day, C., Sarkar, A., Newland, C., Butchar, J., Marsh, C. B., Wewers, M. D., Tridandapani, S., Kanneganti, T.-D., & Amer, A. O.
Venue
PLoS Pathogens
Published
2009-04-03
Volume
5
Issue
4
Pages
e1000361
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W2043753343
Cited by
193
References
6
FWCI
7.80
Type
journal article
Language
en
Open access
gold

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The paper
Akhter, A., Gavrilin, M. A., Frantz, L., Washington, S., Ditty, C., Limoli, D., Day, C., Sarkar, A., Newland, C., Butchar, J., Marsh, C. B., Wewers, M. D., Tridandapani, S., Kanneganti, T.-D., & Amer, A. O. (2009). Caspase-7 Activation by the Nlrc4/Ipaf Inflammasome Restricts Legionella pneumophila Infection. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000361

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